THE RIPID AND LONG-TERM IMPACT OF ACUTE STRESS ON NEUROPLASTICITY. A NOVEL PARADIGM FOR DISSECTION OF STRESS RESPONSE
Tesi di Dottorato
Data di Pubblicazione:
2019
Citazione:
THE RIPID AND LONG-TERM IMPACT OF ACUTE STRESS ON NEUROPLASTICITY. A NOVEL PARADIGM FOR DISSECTION OF STRESS RESPONSE / N. Sala ; tutor: M. Popoli ; co-tutor: L. Musazzi ; coordinatore: A.L. Catapano. Università degli Studi di Milano, 2019 Jun 24. 31. ciclo, Anno Accademico 2019. [10.13130/sala-nathalie_phd2019-06-24].
Abstract:
The response to stressful events is physiologically required to adapt to external challenges.
However, the stress response can either have a ‘pro-adaptive’ outcome, when the response
is efficiently activated and then inactivated, or exert ‘maladaptive’ effects, when the subject
is vulnerable and the response is dysregulated. Unfortunately, it is still unknown what
mechanisms address the individual responses towards pro-adaptive or maladaptive outcome
of stress.
In previous studies we found that acute inescapable footshock (FS)-stress rapidly enhances
depolarization-evoked glutamate release from prefrontal and frontal cortex (PFC/FC)
purified synaptic terminals (synaptosomes), with a mechanism involving rapid, nongenomic
enlargement of the readily releasable pool (RRP) of glutamate presynaptic vesicles.
Moreover, we showed that the same protocol of acute stress induces long-term
atrophy/remodeling of apical dendrites in the same area up to 14 days later, thus suggesting
that the consequences of acute stress are far from being simply acute.
Traditional models of chronic stress reproduce only the endpoint of several changes
occurring in brain and body during the stress response. On the opposite, analyzing short- and
long-term alterations induced by acute stress could be a useful tool to dissect adaptive and
maladaptive components underlying stress response.
Here, we aimed at dissecting the early and delayed alterations induced by a single session of
acute FS-stress, focusing on the putative effectors that trigger towards adaptive/maladaptive
trajectories of the stress response.
We demonstrated that FS-stress increases both glutamate release evoked by depolarization
and RRP size up to 24h after the stress protocol. In parallel, we found that acute FS-stress
exerts different time-dependent molecular alterations in synaptic membranes from PFC/FC.
We then set up a behavioral paradigm that discriminates resilience/vulnerability towards
acute stress, based on stress-induced behavioral alterations.
We demonstrated that the different behavioral phenotypes are associated with specific
functional and molecular alterations in PFC glutamatergic synapses.
Our approach, dissecting rapid and delayed effects of acute stress response, and their
adaptive/maladaptive components, could lead to better understand mechanisms that turn
stress response from a physiological adaptation into maladaptive alterations. The final aim
is to look for the putative effectors of this switch, searching for markers of vulnerability and
novel targets for the therapies of neuropsychiatric disorders.
Tipologia IRIS:
Tesi di dottorato
Elenco autori:
N. Sala
Link alla scheda completa: