Effect of cannabidiol on endocannabinoid, glutamatergic and GABAergic signalling markers in male offspring of a maternal immune activation (poly I:C) model relevant to schizophrenia por Valentina Becerra Gallego
2. INTRODUCTION
Schizophrenia
- Is a serious mental illness that interferes with
a person’s ability to think clearly, manage
emotions, make decisions and relate to others.
- Exhibit structural abnormalities in some
brain regions, like reduced hippocampal
volume and cortical thinning in the prefrontal
cortex.
Symptoms can include: hallucinations,
delusions, negative symptoms (social
withdrawal) and cognitive issues/disorganized
thinking.
The principal treatment for schizophrenia is
antipsychotic drugs (APDs), which are mostly
effective against the positive symptoms (e.g.
hallucinations), but provide minimal benefits
for the negative symptoms (e.g. social
withdrawal) and cognitive deficits.
An imbalance in the main excitatory
(glutamate) and inhibitory (GABA)
neurotransmitter systems in the brain plays a
role in the pathophysiology of schizophrenia.
https://i1.wp.com/metro.co.uk/wp-content/uploads/2017/10/522205044.jpg?quality=90&strip=all&zoom=1&resize=644%2C454&ssl=1
https://www.nami.org/learn-more/mental-health-conditions/schizophrenia
3. GABA
Gamma-aminobutyric acid (GABA) is the
primary inhibitory neurotransmitter known to
counterbalance the action of the excitatory
neurotransmitter glutamate.
Cannabinoids
Cannabidiol (CBD), the main non-
intoxicating phytocannabinoid found in the
cannabis plant, has the potential to alleviate
symptoms across a range of pathological
conditions, including epilepsy, chronic pain,
anxiety and movement disorders.
The endogenous cannabinoid (eCB) system
plays an important role in various
physiological functions as neuroprotection,
synaptic plasticit.
The endocannabinoid system could
represent a therapeutic target for
schizophrenia as a regulator of glutamate
and GABA release via the CB1 receptor
(CB1R)
https://www.ncbi.nlm.nih.gov/pubmed/12662130 http://www.liberaldictionary.com/wp-content/uploads/2019/02/gaba-8322.jpg
4. OBJETIVE
Examine the effects of CBD treatment on eCB), as well as
glutamatergic and GABAergic markers in the brains of poly
I:C offspring that exhibit cognitive deficits.
5. MATERIALES Y MÉTODOS
→ Fundamento: toma de tejido en estudio para
verificar la presencia de las proteínas y los
receptores en estudio.
→ ¿Para qué?: este protocolo de disección
permitió la investigación de la unión del receptor y
los niveles de proteína de los mismos animales.
PROCEDIMIENTO HISTOLÓGICO
6. DENSITOMETRÍA
→ Fundamento: una vez puestas las proteínas
en el gel estas migran según su peso molecular.
→ ¿Para qué?: cuantificación de proteínas y
verificación de la presencia de tales proteínas en
el tejido en estudio
**En el artículo no se realizó la grafica de
densitometría
https://ars.els-cdn.com/content/image/1-s2.0-S1888400816300848-gr1.jpg
7. ELECTROFORESIS DE
PROTEÍNAS SDS-PAGE
→ Fundamento: El método inicialmente
desnaturaliza las proteínas que serán
sometidas a electroforesis. Las proteínas se
ponen en un medio acuoso (gel) y estas
migran según la composición y el tamaño del
poro.
→ ¿Para qué?: se usa comúnmente para
obtener una separación de alta resolución de
mezclas complejas de proteínas.
https://www.sigmaaldrich.com/content/dam/sigma-aldrich/articles/biology/sds-page/sds-page-of-protein.jpg
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517606/
8. WESTERN BLOT
→ Fundamento: primero se realiza
una electroforesis para separar las
proteínas, que luego se transfieren a
otro gel donde se le unen los
anticuerpos con que se reconocerán.
→ ¿Para qué?: detección de una
proteína especifica en una muestra
determinada, mediante el uso de
anticuerpos.
https://ars.els-cdn.com/content/image/3-s2.0-B9780123751560000102-f10-11-9780123751560.jpg
10. No hay diferencias significativas
entre las gráficas y la
cuantificación de proteínas.
11. Alteración de GAD en VEH en
muestra del hipocampo en el
grupo POLY.
No hay más hallazgos
significativos.
12. Alteración de PA
(parvalbumina) en VEH en
muestra del hipocampo en
el grupo POLY.
Alteración de PA
(parvalbumina) en CBD en
muestra del hipocampo en
el grupo CONT.
13. DISCUSSION
Author Concept Yes or not
Khan et al. PV expression is
activitydependent, therefore,
taken together with recent in vitro
findings that CBD can enhance
inhibition elicited by PV+ and
CCK+ GABAergic neurons
Lu and Mackie. CBD treatment did not alter
FAAH protein levels in the PFC or
HPC. FAAH is the primary
enzyme responsible for the
intracellular hydrolysis of AEA in
neurons
Giuffrida et al.
Koethe et al.
AEA may play a protective role
in schizophrenia, especially in the
early stages of the disorder
14. CONCLUSIONS
→ CBD treatment reversed deficits in CB1R binding density in the PFC and
hippocampal GAD67 protein levels in male poly I:C offspring
→ CBD had no effect on FAAH protein levels, NMDAR or GABAAR binding density
in either brain region examined, however, poly I:C offspring did not exhibit deficits in
these markers.