Fundaments of

Neurobiology and Genetics

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During the course of:
“Fundaments of Neurobiology and
Genetics”
topics will be addressed to

UNDERSTANDING OF THE BIOLOGICAL

BASES ON WHICH THE MENTAL
PROCESSES ARE BASED

both in physiological and pathological

condition
It is a big challenge, which has just
opened and which involves experts
of:

• NEUROLOGY
• NEUROPSICHOLOGY
• NEUROPHISIOLOGY
• NEUROANATOMY
• NEUROBIOLOGY
• NEUROPHARMACOLOGY
• NEUROSCIENCE
• A multidisciplinary approach is needed to understand
the biological basis of complex cognitive processes

• The course will be based essentially on the study of

the principles of Neurobiology and Genetics, with
particular attention to everything concerning the
activity of mental processes, both physiologically
and pathologically
The course consists of the following
topics:

a) The scientific method: description of the method used

to proceed scientifically in knowledge; it is universally
accepted and verifiable. Examples of how to proceed to
acquire new data

b) Salient features of living organisms: what

distinguishes, from a biological point of view, a living
organism (man) from non-living matter

c) The macromolecules of life: DNA, RNA and proteins

d) The cell: organelles and their function
the cell cycle and cell cycle control mechanisms; cell division and its
physiological significance (mitosis and meiosis)

e) Genetics: transmission of hereditary characters

- the human karyotype
- genotype and phenotype
- the laws of inheritance
- molecular genetics: how genes are made
- regulation of gene activity
- mutations and genetic variability
- disease-genes
Modul B:

f) Human chromosomal abnormalities: an exploration of genetic and

neurocognitive features
g) Genes and behavior
h) The central nervous system
i) Neurons and neural transmission
i) Neurons mirror

Neurons mirror at work!

 TEXTBOOKS

D. SADAVA-D.M HILLIS-H.C. HELLER-M.R.

BERENBAUM-S. HACKER

Life: the science of Biology

Sinaurer Associates Inc, 2020, 12th edition

Fondamenti Neurobiologici e Genetici
9
dell'attività psichica
 LIVING ORGANISMS

• Are able to maintain the organization

• Are able to reproduce themselves

• Are crossed by a continuous flow of energy

 ENERGY USED BY LIVERS is
“CHEMICAL ENERGY”

• Autotrophic organisms: • Heterotrophic

plants organisms: humans
ENERGY USED BY LIVERS is
“CHEMICAL ENERGY”

photosynthetic
autotrophs heterotrophs
 HUMANS NEED 'TO HAVE A
SUFFICIENT AMOUNT OF ENERGY:

Introduction of food

• Satisfaction of energy needs for maintaining the body's

structures
• Supply of materials for the growth and renewal of the
body's structures
• Need for nutritional elements (H2O, vitamins and
mineral salts) which have no energy value but are
essential nutrients
General Biology
↓
Human Biology
 “Science”
Science is a form of human knowledge characterized
by a method which has two fundamental requirements:

RIGOR
and

OBJECTIVITY
 The "motive" of science
according to Aristotle (IV sec. a.C)
«In fact men have begun to philosophize, now as in
origin, because of wonder; while at first they were
astonished at the simplest difficulties, then, progressing
little by little, they came to pose ever greater problems:
for example, problems concerning the phenomena of
the moon, the sun and the stars, or those concerning
the origin of the entire universe»
(Metaphysic A 2, 982, b11-17)
Different areas of human knowledge have had a scientific
method since their origin.
Others have recently acquired it and are therefore
recognized as "sciences”

For examples:
MATHEMATICAL SCIENCES: Algebra, Geometry
PHYSICAL SCIENCES: Physics, Chemistry, Biology
HUMAN SCIENCES: Psychology, Sociology
Scientific Method
1. OBSERVATION

2. PROBLEM

3. HYPOTHESIS OF SOLUTION

4. VERIFICATION OR REFUTATION

5. CONCLUSION OR THEORY

6. COMMUNICATION
1. OBSERVATION
Careful observation, without prejudice and possibly repeated
of the phenomenon

2. Correct definition of the PROBLEM

It means: a right question asked in the right way. Example:
why does the phenomenon "X" occur in the "Y" conditions
and does not occur in the "Z" conditions? What is the cause
of what I have observed? What relationship does exist
between the "X" stimulus and the "Y" response?
3. Formulation of one or more SOLUTION hypotheses
of the problem
A logical and evaluable attempt to answer the question. Different scientific
hypotheses can be formulated by a single researcher or by several scientists
independently; they are usually updated, modified or discarded on the basis
of further evidence or of observational and experimental new data acquired.

4. VERIFICATION of the HYPOTHESIS

Verification or refutation can be performed by observational or experimental
tests
5. CONCLUSION or proposal of a SCIENTIFIC THEORY

Scientific theory is a hypothesis having predictive value,

supported by numerous and convincing tests, and not
(yet) refuted by any observation contrary to the forecast.

Scientific theories are neither absolute (exempt from

further verification or refutation) nor immutable, but can
be reviewed, corrected, integrated (example: CENTRAL
DOGMA OF BIOLOGY)
6. COMMUNICATION TO THE SCIENTIFIC
COMMUNITY

The "public" nature of science and its

"objectivity" require oral or written
communication of the data, hypotheses,
verifications and any proposed theory
 EXAMPLE OF SCIENTIFIC
RESEARCH
«STUDIES ON THE CHEMICAL NATURE OF THE
SUBSTANCE INDUCING TRANSFORMATION OF
PNEUMOCOCCAL TYPES : INDUCTION OF
TRANSFORMATION BY A DESOXYRIBONUCLEIC ACID
FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III”
Oswald T. Avery, Colin M. MacLeod e MacLyn McCarty

The Rockefeller Institute for Medical Research

New York (USA)
 Diplococcus Pneumoniae and its different
strains
Observations about the morphology of Diplococcus pneumoniae colonies, strains
characteristics and virulence (O.T. Avery and A.R. Dochez, 1917)

Pneumococci
(Diplococcus pneumoniae)

Type II Type III

Strain R Strain S

Non-virulent variant, without a virulent variant, covered by a

polysaccharide capsule, which polysaccharide capsule capable
produces colonies on the plate of preventing phagocytosis,
that look rough (rough = R) which produces colonies with a
smooth surface (smooth = S) and
similar to wax drops
Observations and experiments by
F. Griffith (1928)
EXPERIMENTAL STUDY DESIGN

1. OBSERVATION. «In vivo», the simultaneous

inoculation of living R-type (non-virulent) bacteria and
of heat-killed S-type (virulent) bacteria causes the
death of mice due to bacterial infection. «In vitro», S-
type cell extracts (which contain different chemical
substances present in bacterial cells), added to R-
type cultures, determine a permanent and hereditary
transformation from R-type to S-type.
2. DEFINITION OF THE PROBLEM

What causes the transformation from non-encapsulated and non-virulent R-type

bacteria to S-type, encapsulated and virulent bacteria? What is the "active,

transforming principle" or the substance which induces this hereditary mutation?
What class of chemical compounds does it belong to?

3. HYPOTHESIS

a. A deoxyribonucleic acid (DNA)?

b. A ribonucleic acid (RNA)?

c. A protein?
d. A polysaccharide?
Experiment by Avery, MacLeod
and McCarthy (1943)

29
3. EXPERIMENTAL VERIFICATION

Intact DNA, extracted from S-type bacteria and purified

from lipids, polysaccharides, proteins and RNA, added in
vitro to R-type strains, induces their transformation into
virulent S-type bacteria. This does not happen if the DNA
is treated with hydrolytic enzymes (deoxyribonucleases),
which depolymerize (degrade) the molecule by splitting it
into its monomeric units (enzymatic destruction of DNA)
4. CONCLUSION
a. The DNA molecule "is the fundamental unit of the
transforming principle" which causes the change from R-
type (non-encapsulated and non-virulent) to S-type
(encapsulated and virulent) bacteria

b. The transformation is permanent and hereditary

5. WRITTEN COMMUNICATION
Journal of Experimental Medicine, 1943; 79: 137-158
 CURRENT EXAMPLE

Study of the correlation between specific mutations in the MECP2

gene and the clinical profile of patients affected by Rett syndrome
Fabio RA, Colombo B, Russo S, Cogliati F, Masciadri M, Foglia S, Antonietti A,
Tavian D

Research in Developmental Disabilities 35: 2976-2986, 2014

- Department of Psychology, Catholic University of the Sacred Heart

- Laboratory of Cellular Biochemistry and Molecular Biology-CRIBENS, Catholic University of the

Sacred Heart
 EXPERIMENTAL STUDY DESIGN

1. OBSERVATION.
a. Mutations in the MECP2 gene cause Rett syndrome, a severe
developmental neurodegenerative disorder which affects one in
10.000 children. Genetic heterogeneity has been observed;
pathogenic mutations have also been identified in the CDKL5 and
FOXG1 genes

b. From a clinical point of view, Rett syndrome is very

heterogeneous. At least 5 different clinical presentation can be
described
2. DEFINITION OF THE PROBLEM
What are the factors responsible for the diversity of clinical findings (type, severity
and onset)?
Is there an adequate tool to detect and measure the different degrees of disability
of patients with Rett syndrome?

3. HYPOTHESIS
Different mutations located along the different MECP2 protein domains and
identified in patients are responsible for the high variability of clinical profiles.
The RARS (Rett Assessment Rating Scale) is a suitable tool to express the
variety and severity of the symptomatic areas of patients affected by Rett
syndrome.
4. EXPERIMENTAL VERIFICATION

114 patients with Rett syndrome underwent two different types

of analysis:

a) Genetic analysis: identification of mutations in the MECP2

gene
b) Evaluation of the neuro-cognitive profile of patients by RARS
c) Genotype correlation with RARS results
 SUBSCALE TOPICS
Sensory Visual perception
Auditory perception
Cognitive Attention
Spatial orientation
Temporal orientation
Memory
Eye contact
Verbal skills
Gestures
Motor-Structural e Functional Foot problems
Scoliosis
Walking
Hand use
Emotional Understanding
Expression
Autonomy Toileting
Dressing
Eating and Drinking
Physical Characteristics Breathing Irregularities
Seizures
Bruxism
Abnormal Ocular Movements
Epilepsy
Aerophagy
Muscle Abnormality
Feeding Problems

Behavioural Characteristics Mood Variability

Hyperactivity
Anxiety
Aggression
Frequent MECP2 missense mutations
5. CONCLUSION
a) there is a genotype-phenotype correlation for Rett
syndrome; different mutations of the MECP2 gene determine
different severity in the expression of the syndrome; in
particular, truncating mutations determine a more severe
clinical phenotype in comparison to missense mutations

b) with regard to the most frequent missense mutations, it

can be noted that patients with these mutations have a
specific disability profile in the different areas considered
6. WRITTEN COMMUNICATION
“Recent insights into genotype-
phenotype relationships in patients
with Rett syndrome using a fine grain
scale”

Fabio RA, Colombo B, Russo S, Cogliati F, Masciadri M,

Foglia S, Antonietti A, Tavian D
Research in Developmental Disabilities 35: 2976-2986, 2014

- Department of Psychology, Catholic University of the Sacred Heart

- Laboratory of Cellular Biochemistry and Molecular Biology-CRIBENS,
Catholic University of the Sacred Heart
 I VOLTI DELLA RICERCA

Sara Missaglia
Researcher
Trovare foto

She deals with human rare genetic diseases

“Nothing in life is to be feared, it is only to be understood.

Now is the time to understand more, so that we may fear
less.”
Marie Curie