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Metabolic and Structural Role of Thiamine in Nervous Tissues

Article  in  Cellular and Molecular Neurobiology · November 2008

DOI: 10.1007/s10571-008-9297-7 · Source: PubMed

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Cell Mol Neurobiol (2008) 28:923–931
DOI 10.1007/s10571-008-9297-7
REVIEW
Metabolic and Structural Role of Thiamine in Nervous
Tissues
Abdoulaye Bâ
Received: 9 March 2007 / Accepted: 30 June 2008 / Published online: 19 July 2008
Ó Springer Science+Business Media, LLC 2008
Abstract In the literature, previous descriptions of
the role of thiamine (B1 vitamin) focused mostly on
its biochemical functions as a coenzyme precursor of
some key enzymes of the carbohydrate metabolism.
This report reviews recent developments on the
metabolic and structural role of thiamine, e.g., the
coenzyme and noncoenzyme functions of the vita-
min. Taking into account analysis of our
experimental data relating to the effects of thiamine
deficiency on developing central nervous system
(CNS) and data available in literature, we seek to
establish a clear difference between the metabolic
and structural role of thiamine. Our experimental data
indicate that the specific and nonspecific effects
express two diametrically diverse functions of thia-
mine in development: the nonspecific effects show up
the metabolic consequences of thiamine deficiency
resulting in apoptosis and severe cellular deficit;
inversely, the specific effects announced the struc-
tural consequences of thiamine deficiency, described
as cellular membrane damage, irregular and ectopic
cells. The review highlights the existence of non-
coenzyme functions of this vitamin through its
interactions with biological membranes.
A. Bâ (&)
Université de Cocody, UFR Biosciences, 22 BP 582,
Abidjan 22, Ivory Coast
e-mail: abdouba3000@hotmail.com
Keywords Thiamine deficiency

Developing brain
Metabolic and structural role
Introduction
The brain uses glucose as a primary fuel for energy
generation. Glucose gains entry into the brain by
facilitated diffusion across the blood–brain barrier
(Rao and Seaquist 2006). Roughly, 30% of the
glucose absorbed by the brain undergoes a complete
oxidation through the tricarboxylic acid cycle (Sie-
bert et al. 1986). Three enzymatic systems, essential
for the cerebral metabolism of glucose, depend on
thiamine (B1 vitamin): The mitochondrial pyruvate
and a-ketoglutarate dehydrogenases complexes and
the cytosolic transketolase (Martin et al. 2003). These
three enzymes use, as cofactor, the thiamine pyro-
phosphate (TPP) which accounts for 80% of total
thiamine present in nervous tissues (Ishii et al. 1979).
In the literature, the major part of actions of the
thiamine described in nervous tissues is limited to
those metabolic aspects which show up the co-
enzymatic function of the vitamin (Butterworth
1987). However, literature that takes an interest in
the structural role of thiamine is growing. So,
thiamine interferes with the membrane structure
and function (Tanaka and Cooper 1968; Itokawa
et al. 1972; Goldberg et al. 2004), acts against
agents-induced cytotoxicity (Bâ et al. 1996; Aberle
123
924
et al. 2004) and fixes membrane sites (Czerniecki
et al. 2004; Spector and Johanson 2007). Those
observations illustrate the noncoenzymatic function
of the vitamin. We reported the metabolic to be
different from the structural role of thiamine in
nervous tissues, constantly (Bâ et al. 1996, 2005; Bâ
2005). This review attempts through discussion to
differentiate the metabolic from structural role of
thiamine, in other words, to separate the coenzyme
and noncoenzyme functions of the vitamin.
Studies of the thiamine metabolism variations are
often achieved according to chronic alcoholism.
Chronic alcoholism weakens the metabolism of
thiamine by a reduction of the rate of enzymes
dependent on the vitamin (Butterworth 1989). In
addition, the Fetal Alcohol Syndrome (FAS) was
commonly described in children born to severely
alcoholic mothers (Jones and Smith 1973). The
Intrauterine Growth Retardation (IUGR), a frequent
concomitant of FAS, was suggested to result from the
effects of ethanol-induced thiamine deficiency
(Rœcklin et al. 1985).
In our studies, we investigated in the rat, exper-
imental models of FAS (Bâ et al. 1996, 1999) and
IUGR (Bâ 2005; Bâ et al. 2005). For further under-
standing of the role of the thiamine in nervous tissues,
we have studied the effects of thiamine deficiency on
the developing central nervous system (CNS), (Bâ
2005; Bâ et al. 2005). Thus, thiamine deficiency was
induced during three main periods of the rat CNS
ontogenesis. Females were fed with a thiamine
deficient diet during the periods of gestation and
lactation; fetuses were exposed alternatively to pre-,
peri- or postnatal thiamine deficiency. Thereafter, the
effects of maternal thiamine deprivation were
assessed on the development of psychomotor and
sensory functions in the offspring: seven different
developmental abilities (exploratory activity, emo-
tional reaction, hind paws lifting reflex, wire grasping
times, crawling and leap execution latencies, and
nociception) were recorded in the offspring from the
10th to the 45th postnatal day (Bâ and Seri 1993,
1995), to assess the specific and nonspecific effects of
maternal thiamine deficiency on fetal brain (Bâ
2005).
Control dams (C) received regular diet containing
thiamine during gestation and lactation. B1 lack-
induced anorexia in thiamine deficient dams (TD) was
reproduced in pair-fed dams (PF) which received a
123
Cell Mol Neurobiol (2008) 28:923–931
reduced quantity of regular diet matched to the TD
dams’ consumption. The malnutrition generated by
every pattern of thiamine deficiency was controlled
by its own PF group. For each pattern of thiamine
deficiency, we made multiple comparisons between
C-TD-PF data recorded on the corresponding off-
spring (Bâ 2005): Specific effect, e.g., effect caused
by thiamine lack per se was diagnosed if
C = TD = PF; nonspecific effect, e.g., effect of
malnutrition that comes with a thiamine deprivation
was identified when C = TD = PF. On the 45th
postnatal day, histologic studies were done on the
brains of the offspring and the structure of the
hippocampus was examined (Fig. 2a). Average reduc-
tion rate in nuclear size and density was assessed
following each pattern of thiamine deficiency, within
the dentate gyrus and the fields CA4, CA3 and CA1 of
the hippocampus (Fig. 2a), (Bâ et al. 2005).
Developmental Thiamine Deficiency
Figure 1 summarizes profiles from four typical
effects of developmental thiamine deficiencies on
the CNS, gathered through our previous studies
(Bâ 2005; Bâ et al. 1999, 2005), e.g., specific and
nonspecific effects, cellular death and atrophy, which
were statistically assessed from prenatal to postnatal
periods.
Developmental Thiamine deficiency
70
60
50
Non-specific effects
Percentages
40 Specific effects
Cellular death
30 Cellular atrophy
20
10
0
Prenatal Perinatal Postnatal
Thiamine deficiency
Fig. 1 Profiles of four typical effects of developmental
thiamine deficiency on the CNS. Extract from data published
elsewhere (Bâ 2005; Bâ et al. 1999, 2005)
Cell Mol Neurobiol (2008) 28:923–931 925

Our results show that the percentage of functions

altered by the specific lack of B1 vitamin increases
from prenatal (28.57%) to perinatal (42.85%) and to
postnatal periods (57.14%). Inversely, the percentage
of functions altered by the nonspecific effects of
thiamine deficiency decreases from prenatal
(60.14%) to perinatal (35.31%) and postnatal periods
(14.32%), (Fig. 1), (Bâ 2005).
It appears also that the rate of cellular death,
resulting from thiamine deficiency, decreases pro-
gressively from prenatal (39.97%) to perinatal
(26.75%) and postnatal periods (14.92%), whereas
cellular atrophy does not seem to show any percep-
tible variations from prenatal (7.97%) to peri-
(12.95%) and postnatal (10.77%) periods (Fig. 1),
(Bâ et al. 2005).
Statistical analysis shows that the specific and
nonspecific effects of thiamine deficiency, on the
functional development of the CNS, are negatively
correlated (R = -0.9988, t = 20.39, P \ 0.025).
Cellular death exhibits a positive correlation with
the nonspecific effects of thiamine deficiency
(R = 0.9998, t = 49.99, P \ 0.01) and negative with
the specific effects of that deficiency (R = -0.9994,
t = 28.85, P \ 0.025), during development. Cellular
atrophy does not show any significant correlation
with either the nonspecific effects (R = -0.5997,
t = 0.75, P [ 0.1) or the specific effects of thiamine
deficiency (R = 0.5606, t = 0.67, P [ 0.1).
For a better illustration of our goal, we compare in
Fig. 2c and d, the effects of pre- and postnatal
thiamine deficiencies on qualitative morphological
alterations assessed from the hilar CA3 pyramidal
cells of the hippocampus (Fig. 2a). Figure 2c shows
that prenatal thiamine deficiency was characterized
by a singular deficit of CA3 pyramidal cells com-
Fig. 2 (a) Parasagittal sections of the left ventral hippocampus
parative to regular diet (Fig. 2b), without any direct in 45-day-old rats. Paraffin 10 lm thick sections were stained
impact on nucleus or cytoplasm shape. On the with a combination of hematoxylin–eosin and indigo carmine;
contrary, postnatal thiamine deficiency exhibited sections of the midtemporal hippocampus were assessed. (a)
The arrowhead demarcates the CA3 region and the arrow
more cornered, irregular and sparse pyramidal cells
denotes the CA1 region; field CA4 is enclosed by broken lines;
in the hippocampal CA3 field (Fig. 2d), comparative bar = 100 lm. P: pyramidal cell layer; G: granule cell layer;
to regular diet (Fig. 2b). Figure 2d shows typical sm: stratum moleculare; sr: stratum radiatum; so: stratum
features of severe postnatal thiamine deficiency with oriens. (b–d) Effects of developmental thiamine deficiencies on
the hilar CA3 pyramidal cells of the hippocampus. (b) Controls;
characteristic breakings on cellular membranes illus-
(c) Prenatal exposed pups; (d) Postnatal exposed; bar = 20 lm
trated by more cornered than pyramidal shaped cells
in the hippocampal CA3 field. Moreover, postnatal condensed chromatin (Fig. 2d), (Kerr et al. 1994). It
thiamine deficiency resulted in a significant increase is obvious that prenatal thiamine deficiency kills cells
in pro-apoptotic-related morphological and biochem- metabolically, while postnatal thiamine deficiency
ical changes characterized by cells containing damages cells structurally.

123
926
How to interpret the specific and nonspecific
effects of thiamine lack on the developing CNS?
Metabolic Role of Thiamine
Our studies indicate that specific and nonspecific
effects express two diametrically diverse functions of
thiamine in development (Fig. 1). The percentage of
functions altered by the nonspecific effects of thia-
mine deficiency decreases from prenatal (60.14%) to
perinatal (35.31%) and postnatal periods (14.32%),
(Bâ 2005); these periods overlap the moments of
cellular migration, proliferation and developmental
apoptosis that is active shortly after that (Bâ et al.
2005). Concomitantly, the rate of cellular death
decreases progressively from prenatal (39.97%) to
perinatal (26.75%) and postnatal periods (14.92%),
(Fig. 1), (Bâ et al. 2005). Our present results con-
firmed a significant positive correlation between
cellular death and the nonspecific effects of develop-
mental thiamine deficiency. The nonspecific effects
would be assigned to the undernourishment that
comes with the thiamine deficiency. Consequently,
developmental thiamine deficiency-induced cellular
death would be caused by the nonspecific effects of
that deficiency, e.g., the malnutrition that comes with
the vitamin lack (Bâ et al. 2005). The nonspecific
effects should be expressed by the metabolic role of
thiamine. How thiamine (B1 vitamin) deficiency
induces cellular death?
To explain mechanisms of cellular damage and
death, most of investigations have focused on general
metabolic effects of thiamine deficiency like ultimate
actions of B1 vitamin lack. For instance, metabolic
reduction of thiamine-dependent enzymes should be
the starting box of any peripheral and central neur-
opathies (Butterworth 1989). However, following
thiamine deficiency, thiamine-dependent enzymes,
i.e., a-ketoglutarate and pyruvate dehydrogenases
complexes, as well as non-thiamine-dependent
enzymes, i.e., succinate and malate dehydrogenases
of the tricarboxylic acid cycle are reduced in the
brains of mice (Bubber et al. 2004). Another example
is the Wernicke’s encephalopathy diagnosed in
chronic alcoholics, described as a constellation of
selective neuropathological lesions occurring in the
brain of patients in which thiamine deficiency was
indexed as the causal factor of selective neuronal loss
123
Cell Mol Neurobiol (2008) 28:923–931
(Navarro et al. 2005). However, the cause of Wer-
nicke’s encephalopathy is thiamine deficiency as a
result of any nutritionally deficient state, and the
disease could not be confined only to alcoholics
(Donnino et al. 2007). In addition, thiamine defi-
ciency induces quantitative, distinct inflammatory
responses and oxidative stress in vulnerable and
nonvulnerable regions that lead to cellular loss
(Karuppagounder et al. 2007).
Several basic mechanisms underlying thiamine
deficiency-induced apoptosis and neurodegeneration
have been reported recently. These mechanisms
include: (i) Compromised energy production and
lactic acidosis (Martin et al. 2003; Navarro et al.
2005); (ii) excess levels of free radicals and oxidative
stress (Gibson and Blass 2007; Frank et al. 2008);
(iii) changes in microglia making a start on neuro-
degeneration (Ke and Gibson 2004); (iv) the voltage-
dependent K + membrane conductance alteration
(Oliveira et al. 2007); (v) cellular membrane break-
ing (Bâ et al. 1996); (vi) the mitochondrial caspase
3-mediated apoptosis (Chornyy et al. 2007); (vii)
translocation of amyloid precursor protein C-terminal
fragments into the nucleus (Karuppagounder et al.
2008). Seemingly, most of these mechanisms are
membrane-mediated effects of thiamine deficiency.
In addition, experimental thiamine deficiency is a
model of impaired oxidative metabolism (Ke and
Gibson 2004). Thiamine-dependent mitochondrial
dehydrogenase complexes produce oxygen free
radicals (Gibson and Blass 2007). Oxygen-dependent
free radical is generated during substrate turnover in
the krebs cycle and its reaction with molecular
oxygen results in the continuous production of
reactive oxygen species (ROS) under aerobic condi-
tions (Frank et al. 2008). Overproduction of ROS
(arising from mitochondrial electron-transport chain)
results in oxidative stress which damages cellular
structures, including lipids and membranes, proteins,
and DNA (Valko et al. 2007). Indeed, thiamine can
act as a free radical scavenger (Gibson and Blass
2007). Free-radicals derive from mitochondrial
dysfunction (Mancuso et al. 2007). Alteration of
mitochondrial TPP transporter causes neural tube
closure defect and results in Amish Lethal Micro-
cephaly (Lindhurst et al. 2006). Thiamine deficiency
which provokes mitochondrial dysfunction with
increased glycolysis, increased lactate dehydrogenase
and focal lactate accumulation (Navarro et al. 2005),
Cell Mol Neurobiol (2008) 28:923–931
results in a significant release of free radicals which,
in turn, diminishes reduced glutathione (GSH) and
other defense systems against oxidative stress at the
origin of major neurodegenerative diseases. For
instance, Prion diseases or Transmissible Spongiform
Encephalopathies (TSE) are connected with a con-
genital and dramatic loss of antioxidant defense
proteins in the brain (Brown 2005). Another meta-
bolic disease related to thiamine and oxidatif stress is
diabetes. Complications in diabetes mellitus are
partially mediated by enhanced formation of reactive
oxygen species (Schmid et al. 2008), similarly to
thiamine deficiency. Benfotiamine, a lipophilic
derivative of thiamine with better bioavailability,
alleviates diabetes-induced cerebral oxidative stress
(Wu and Ren 2006). Benfotiamine prevents oxidative
stress-induced DNA damage (Schmid et al. 2008)
and corrects defective replication in human umbilical
vein endothelial cells cultured in high glucose
(Pomero et al. 2001). The thiamine derivative pro-
drug prevents micro- and macrovascular endothelial
dysfunction and the oxidative stress accompanying
that dysfunction in type 2 diabetes (Stirban et al.
2006). Both thiamine and benfotiamine correct
increased apoptosis due to high glucose in cultured
vascular cells (Beltramo et al. 2004). These observa-
tions suggest that oxidative damage is critical to the
pathogenesis of thiamine deficiency (Gibson and
Blass 2007). From the analysis of the implication of
B1 vitamin lack in different metabolic diseases, we
propose an integrated mechanism for the metaboli-
cally thiamine deficiency-induced cellular death
which starts with extended free radicals damage in
the brain. Increased free radicals production related to
thiamine deficiency launch cellular membrane dam-
age, including lipoperoxydation (Bâ et al. 1999;
Valko et al. 2007), alteration of neuron ion channels
and transporters and microglia changes. Persistent
free radicals produced by severe thiamine deficiency
break cellular membrane (Bâ et al. 1996, 1999)
which signals a cascade of cellular death pathways
via intracellular messengers, like intracellular caspase
3-mediated apoptosis, toward the nucleus. Caspase 3
had been identified among the first components of the
programmed cellular death machinery (Zakeri and
Lockshin 2008). Subsequent nucleolysis machinery
includes, among others, translocation of proteins
carboxy-terminal fragments into the nucleus of
neurons (Karuppagounder et al. 2008). The cytosolic
927
pH changes by focal lactate acidosis should be an
endogenous factor to launch and/or to amplify the
cascade of cellular death pathways.
Structural Role of Thiamine
Our results also indicate a negative correlation between
cellular death and the specific effects of thiamine
deficiency, which increase over postnatal days. These
observations suggest that specific effects bribe altera-
tions in membrane processes which develop postnatally,
e.g., cellular differentiation, synapses formation, axonal
growth, and myelinogenesis (Bâ 2005). In example, it
appears in our studies that structural alterations consti-
tute the main effects of postnatal thiamine deficiency,
including more cornered, irregular and sparse pyramidal
cells in the hippocampal field CA3, comparative to
either regular diet or prenatal thiamine deficiency. These
structural changes were accompanied by biochemical
modifications characterized by cells containing con-
densed chromatin visible in Fig. 2d.
Indeed, a number of experimental issues reveal
that thiamine interferes with the membrane structure
and function, acts against agents-induced cytotoxicity
and highlight the presence of thiamine-binding sites
on biological membranes.
Membrane Structure and Function
The interference of thiamine with the structure and
function of biological membrane becomes obvious.
Some previous studies reported that thiamine would
be an active component of axoplasmic, mitochondrial
(Tanaka and Cooper 1968; Itokawa et al. 1972) and
synaptosomal membranes (Matsuda and Cooper
1981). It undergoes axonal anterograde transportation
and retrograde as well (Tanaka et al. 1973; Bergquist
and Hanson 1983), and intervenes in the synaptic
transmission (Siegel et al. 1989). For instance, Thi-
amine was reported to fix membrane ion channels and
to modify their activity (Tallaksen and Tauboll 2000).
Thus, thiamine deficiency provoked a significant
decrease in the voltage-dependent K+ membrane
conductance of cerebellar granule neurons, by sup-
pression of A-type K+ channels mainly, that leads to
neuronal cell damage and loss (Oliveira et al. 2007).
The consequence is the significant reduction of
nervous conduction speed (Goldberg et al. 2004),
123
928
followed by the blocking of the nervous fiber action
potential by the pyrithiamine, an antagonist of the
thiamine (Goldberg and Cooper 1975). Thiamine
deficiency should provoke further disturbances in
nervous electrical activities by the alteration of
myelinogenesis (Trostler et al. 1977; Reddy and
Ramakrishnan 1982), resulting in reduction of the
diameter of myelinic fibers (Claus et al. 1985).
Membrane Stability
It seems obvious that thiamine exerts stabilizing
interactions on the biological membranes. Investiga-
tions on the role of thiamine during developmental
processes confirm physiologic protecting actions of
thiamine on nervous cells and others tissues. For
instance, thiamine stabilizes the membrane of newly
generated neuronal cells during embryogenesis and
slows the programmed cell death that is the devel-
opmental apoptosis (Wang et al. 2000; Bâ et al.
2005). In addition, the study on differential altera-
tions in the distribution of three phosphatase
enzymes, during early pregnancy in the rat, has
shown that thiamine contributes to the process of
plasma membrane transformation of uterine epithelial
cells (Bucci and Murphy 1999). However, most of the
studies highlight the capacity of thiamine to protect
cellular membrane against alcohol-induced cytotoxic
effects. Thus, thiamine prevents or reduces alcohol-
induced damages of hippocampal CA1 pyramidal
cells in rat CNS (Wenisch et al. 1996). In addition,
pyrithiamine and ethanol-induced cytotoxicity is
prevented in cerebellar slice cultures co-exposed to
thiamine (Mulholland et al. 2005). For the former
explanations of the observed alcohol-thiamine antag-
onism on cytotoxicity, Bâ et al. (1996) hypothesized
that B1 vitamin acts against the effects of ethanol on
fluidity, and therefore increases membrane stability
(Bâ et al. 1996). To explain the mechanisms of action
on biological membranes, thiamine was suggested to
exert a nonspecific stabilizing interaction on the
axonal membrane (Goldberg et al. 2004). However, a
recent study has reported the specificity of vitamin
B1, and not B6 or B12, in protecting cardiac
ventricular myocytes against the effects of alcohol
metabolite, the acetaldehyde-induced cytotoxicity
and apoptotic cell death (Aberle et al. 2004). The
last hypothesis states the problem of the existence of
thiamine-binding sites on biological membranes.
123
Cell Mol Neurobiol (2008) 28:923–931
Membrane Sites
There is an increasing argumentation reporting the
existence of thiamine-binding sites on biological
membranes (thiamine triphosphate) different from its
membrane carrier sites (thiamine diphosphate). Con-
trary to the thiamine triphosphate (TTP) that fixes on
the cellular surface, thiamine diphosphate (TDP) was
fixed by a specific intra membrane carrier and
transported into the cytosol actively (Spector and
Johanson 2007). The first allusion to the existence of
thiamine-binding sites on biological membranes,
different from intra membrane carrier, was suggested
trough the reversal of the effects of thiamine
deficiency by antioxidants, suggesting that thiamine
may act as a site-directed antioxidant (Gibson and
Zhang 2002). Recent disclosure in peroxisomes of
TDP-dependent enzyme that catalyzes alpha-oxida-
tion of straight chain fatty acids makes possible the
existence of membrane surface sites fixing thiamine
(Sniekers et al. 2006; Fraccascia et al. 2007).
Through our developmental studies, we reported that
the specific need of B1 vitamin increased in nervous
tissues during ontogenesis and corresponded to the
post-natal development of membrane processes (Bâ
2005). An assumption is that the developing mem-
branes should generate an increasing surface
distribution of thiamine-binding sites insuring their
stability. That assumption was corroborated by
previous studies reporting changes of thiamine
metabolism in the rat brain during postnatal devel-
opment (Matsuda et al. 1989). Indeed, from birth to
3 weeks, the activity of thiamine diphosphatase
(TDPase) developped more strongly in the liver than
in the brain, while that of thiamine triphosphatase
(TTPase) increased more powerfully in the brain than
in the liver (Matsuda et al. 1989). Thus, microsomal
and soluble TTPase in the cerebral cortex and
cerebellum increased after birth and plateaued at
3 weeks; the increase of the enzyme activity was
more significant in the former tissue than in the latter
(Matsuda et al. 1989). These observations suggest
that in the nervous tissue, TTPase activity should
interfere with the post-natal development of mem-
brane processes. Makarchikov et al. (2003) reported
that TTP was widely distributed from prokaryotes to
mammals and may have a basic role in cell metab-
olism or cell signaling. For instance, the main electric
organ of Electrophorus electricus is particularly rich
Cell Mol Neurobiol (2008) 28:923–931
in TTP, which represents 87% of the total thiamine
content in this tissue (Bettendorff et al. 1987). Such
an observation suggests TTPase implication in the
restoration of membrane stability after intense elec-
trical activity. Thus, TTP seems to be essentially
associated with neurons: In rat brain, the amount of
TTP is about five times higher in neurons than in
astrocytes (Bettendorff et al. 1991). Indeed, the
membrane-associated enzyme form (TTPase) may
play a physiologic role other than TTP hydrolysis in
mammalian tissues (Szyniarowski et al. 2005). In
vertebrate tissues, TTPase may act as a phosphate
donor for the phosphorylation of certain proteins; that
may be part of a new signal transduction pathway
(Czerniecki et al. 2004). Thiamine deficiency
decreases membrane-associated TTPase activity
(Iwata et al. 1974). Membrane-associated TTPase is
affected by proteolytic enzymes (Bettendorff et al.
1987). Distribution of TTPase activity, typical of
thiamine-binding proteins in cellular structures, was
studied (Ianchii et al. 2003; Czerniecki et al. 2004).
TPPase immunocytochemical labeling showed the
strongest staining in hippocampal pyramidal neurons,
as well as cerebellar granule cells and Purkinje cells.
Immunoreactive cells were distributed throughout
cerebral cortical gray matter and the thalamus. White
matter was not significantly labeled. TTPase immu-
noreactivity seems to be located mainly in the
cytoplasm and dendrites (Czerniecki et al. 2004).
Subcellular structures precipitated as microsomal
fractions, e.g., endoplasmic reticulum and vesicular
parts of plasma membranes were encrusted with TTP-
binding proteins (Ianchii et al. 2003). Thus, there are
several evident lines allowing the membrane-associ-
ated thiamine triphosphatate-binding proteins to be
indexed like a stabilizing factor of the structure and
function of cellular membrane. TTP-binding proteins
should exert cytoprotective signals that maintain
tissue homeostasis and counteracts apoptotic agents
like free radicals. The regional vulnerability of
central structures should be based on the lack or
failure of TTP-binding proteins systems protection
against radicals irradiation or others cytotoxic agents.
Growth Factor?
Our results show that thiamine does not exert any
main role on cellular growth. Cellular atrophy did not
929
show any significant correlation neither with nonspe-
cific, or specific effects of developmental thiamine
deficiency. These results indicate that the lack of
thiamine is not a causative factor of cellular atrophy.
Thus, thiamine cannot be classified like a growth
factor. In recent studies, determination of the impact
of the dietary concentration of 5 B vitamins (ribofla-
vin, niacin, pantothenic acid, cobalamin, and folacin)
showed no influence on pig growth performance; the
greater need for these vitamins is not associated with
greater dietary energy intake or body energy accre-
tion rate, but is potentially due to shifts in the
predominant metabolic pathways (Stahly et al. 2007;
Böhmer and Roth-Maier 2007).
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