Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke

Abstract

Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicletreated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24 h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia.

Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia

“…Omega-3 is known to play a role in the regulation of neurotrophins like BDNF and its receptor Trk-B, which are involved in spatial learning and memory (Bhatia et al 2011). Several studies have reported enhanced hippocampal neurogenesis along with increased levels of BDNF levels following omega-3 PUFAs treatment (Blondeau et al 2009, Venna et al 2009). …”

Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure

“…Subchronic treatment with three sequential injections of LIN has been previously demonstrated to increase the endogenous expression of mature brain-derived neurotrophic factor (BDNF) levels in neural stem cells, cultured hippocampal neurons and in cortex and hippocampus. Also in cortex and hippocampus, LIN increases synaptogenesis, synaptic function and increases neurogenesis in the subgranular zone of the dentate gyrus of the hippocampus in naïve mice (Blondeau et al 2009). This treatment schedule also significantly reduced infarct volume in the middle cerebral artery occlusion model of stroke and was associated with a significant improvement in animal survival (Blondeau et al 2009).…”

The role of omega-3 fatty acids in adult hippocampal neurogenesis

“…Several studies have reported enhanced hippocampal neurogenesis in parallel with increase levels of BDNF levels following omega-3 PUFA treatment (Cysneiros et al, 2010;Venna et al, 2009;Blondeau et al, 2009). For example, three sequential injections of alinolenic acid significantly enhances adult hippocampal neurogenesis in mice, and increases in the expression of BDNF in hippocampal neurons and cortical and hippocampal tissue (Blondeau et al, 2009). In this study, the treatment also significantly increases the expression of proteins critical for synaptogenesis and synapse function, syntophysin-1, VAMP-2 and SNAP-25, and proteins supporting glutamatergic neurotransmission, V-GLUT-1 and V-GLUT-2.…”