GLUTAMATE-DEPENDENT HIPPOCAMPAL SYNAPTIC REMODELLING DECREASES CELL ADHESION MOLECULES EXPRESSION: CORRELATION WITH AN EXPERIMENTAL MODEL OF DEPRESSION

PODESTÁ MF; LORENZO LÓPEZ, JR; CODAGNONE, M; LÓPEZ, M; BRUSCO, A; WIKINSKI, S; REINÉS, A

Huerta Grande, Cordoba

Congreso; Primera Reunión Conjunta de Neurociencias (IRCN); 2009

Sociedad Argentina de Neurociencias (SAN)

Dendritic atrophy of hippocampal CA3 neurons found in experimental depression is 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 studied the ultrastructural morphology of synapses and cell adhesion molecule expression in LH animals. In primary hippocampal neurons we analyzed the impact of GLU hyperstimulation on synapse morphology and synaptic protein expression. EM studies showed increased synaptic cleft width at the CA3 synapses of LH animals. While in control rats synaptic vesicles per synapse (SV/S) ratio was homogenous, in LH group SV/S ratio presented extreme low or high values. Postsynaptic density (PSD) morphology was altered in LH rats, while PSD length decreased; PSD width increased rendering similar values in total area. LH rats also showed decreased immunostaining for NCAM and PSA-NCAM, cell adhesion molecules implicated in plasticity and expressed by GLU neurons. In vitro, hippocampal primary neurons exposed to GLU 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. These results support the hypothesis that glutamatergic hyperactivity in LH rats could reduce cell adhesion molecule expression leading to decreased synaptic connectivity in hippocampal CA3. Grants PICT34397, UBACYT B422