Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

Abstract

The anticonvulsants that are currently available modulate the activity of neuronal receptors and ion channels, which are equally involved in apoptotic pathways. We investigated the hypothesis that gabapentin (GP), an anticonvulsant without effect on glutamate receptors acting as GABA analog, has neuroprotective properties. For comparison, we chose topiramate (TPM), which has been reported to be neuroprotective via AMPA receptors blockade. For this purpose, we used rat cerebellar granule neuron (CGN) cultures and we triggered apoptosis independent of glutamate receptors with staurosporine, a broad-spectrum protein kinase inhibitor. GP at therapeutic range concentration significantly increased cell viability in CGN cultures maintained in physiological KCl concentration and reversed apoptosis induced by staurosporine. Blockade of NMDA or AMPA receptors by MK801 or NBQX, respectively, did not alter GP neuroprotection, which was reversed instead by GABA. In contrast, protective effect of TPM on STS-treated CGN cultures was annihilated by NBQX, and not altered by MK801 or GABA. Treatments with neuroprotective concentrations of GP or TPM did not modify the expression of neuronal cell adhesion molecule or synaptophysin or the morphological aspect of neuronal endings. In summary, we report that GP is neuroprotective through glutamate-receptor independent mechanisms and without alteration of neuronal plasticity markers, which makes it a possible candidate for clinical neuroprotection trials.

Gabapentin and its salicylaldehyde derivative alleviate allodynia and hypoalgesia in a cisplatin-induced neuropathic pain model

“…It is possible therefore that multiple mechanisms are responsible for the anticonvulsant, anxiolytic, neuroprotective (Baydas et al, 2005) and antinociceptive activity observed in different animal models. In the context of the GBP effect on thermal hypoalgesia, a neuroprotective action mediated by glutamate receptorindependent mechanisms has been reported (Popescu et al, 2013). There is also evidence that GBP improves nerve remyelination after chronic sciatic nerve constriction injury (Câmara et al, 2015).…”

The effects of gabapentin and ethanol on the regulated cell death of astrocytes in primary culture

“…Modulation of α2δ-1 transmitted signalling also influences apoptotic cell death, anatomic reorganization, excitatory synaptogenesis, astrocytosis, and network hyperexcitability in a model of insultinduced cortical malformation (12). Recent studies revealed that gabapentin protects cultured neurons from staurosporine-induced apoptosis, and reduces the intensity of reactive gliosis, both in microglial and astroglial cells (13). Gabapentin has also been found beneficial in the treatment of alcohol withdrawal in alcoholics (14,15) and has a selective action in decreasing the convulsive and anxiety related signs of ethanol withdrawal in mice (16).…”