IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Glutamate and psa-ncam dependent hippocampal synaptic remodelling: Correlation with an experimental model of depression and its pharmacological treatment
Autor/es:
PODESTA MF, CODAGNONE M, LORENZO LOPEZ JR, LOPEZ M, BRUSCO A, WIINSKI S, REINES AG
Lugar:
San Diego
Reunión:
Congreso; 40 Annual Meeting Society for Neuroscience; 2010
Institución organizadora:
Society for Neuroscience
Resumen:
Dendritic atrophy of hippocampal CA3 neurons and dysfunction of hippocampal
plasticity have been proposed to play a critical role in the pathophysiology of
depression and are both probably related to excessive glutamate (GLU) release.
Based on our previous results showing decreased hippocampal synaptophysin (SYN)
and PSD-95 expression in animals exposed to the learned helplessness (LH)
paradigm, an experimental model of depression, we examined the synapse
morphology and cell adhesion molecule expression in the LH paradigm, with and
without fluoxetine (FLX) treatment. In primary hippocampal neurons we analyzed
the impact of GLU hyperstimulation on synapse morphology and synaptic protein
expression. Electron microscopy studies showed increased synaptic cleft width at
the CA3 synapses of LH animals. While postsynaptic density (PSD) length
decreased, PSD width increased rendering similar values in total area. In LH
group synaptic vesicles per synapse (SV/S) ratio presented extreme low or high
values, whereas in control rats SV/S ratio was homogenous. These results are
compatible with plastic and synaptic connectivity alterations. Interestingly LH
rats also showed decreased CA3 immunostaining for NCAM and PSA-NCAM, cell
adhesion molecules implicated in plasticity and expressed by GLU neurons. In
vitro, GLU hyperstimulation of hippocampal neurons in culture presented reduced
MAP-2, NCAM and PSA-NCAM immunostaining. Whereas PSD-95 and SYN puncta number
diminished, individual puncta size was not modified for PSD-95 and was increased
for SYN. Our results indicate that excessive neuronal exposure to GLU induces
synaptic changes in vitro that resemble those observed in LH animals.
Surprisingly FLX treatment of LH rats recovered synaptic cleft width values,
increased total synaptic vesicle number particularly by augmenting reserve
synaptic vesicles. Also strongly reduced NCAM and increased PSA-NCAM levels in
CA3 in LH animals. Results support the hypothesis that GLU hyperactivity in the
CA3 of LH rats could reduce cell adhesion molecule expression and that FLX
action could involve PSA-NCAM dependent synaptic remodelling that might lead to
neuronal connectivity normalization.