Aging is a complex biological process that increases the risk of age-related cognitive degenerative diseases such as dementia, including Alzheimer's disease (AD), Lewy Body Dementia (LBD), and mild cognitive impairment (MCI). Even non-pathological aging of the brain can involve chronic oxidative and inflammatory stress, which disrupts the communication and balance between the brain and the immune system. There has been an increasingly strong connection found between chronic neuroinflammation and impaired memory, especially in AD. While microglia and astrocytes, the resident immune cells of the central nervous system (CNS), exerting beneficial effects during the acute inflammatory phase, during chronic neuroinflammation they can become more detrimental. Central cholinergic circuits are involved in maintaining normal cognitive function and regulating signaling within the entire cerebral cortex. While neuronal-glial cholinergic signaling is anti-inflammatory and anti-oxidative, central cholinergic neuronal degeneration is implicated in impaired learning, memory sleep regulation, and attention. Although there is evidence of cholinergic involvement in memory, fewer studies have linked the cholinergic anti-inflammatory and anti-oxidant pathways to memory processes during development, normal aging, and disease states. This review will summarize the current knowledge of cholinergic effects on microglia and astroglia, and their role in both anti-inflammatory and anti-oxidant mechanisms, concerning normal aging and chronic neuroinflammation.

The Australian rainforest is a rich source of medicinal plants that have evolved in the face of dramatic environmental challenges over a million years due to its prolonged geographical isolation from other continents. The rainforest consists of an inherent richness of plant secondary metabolites that are the most intense in the rainforest. The search for more potent and more bioavailable compounds from other plant sources is ongoing, and our short review will outline the pathways from the discovery of bioactive plants to the structural identification of active compounds, testing for potency, and then neuroprotection in a triculture system, and finally, the validation in an appropriate neuro-inflammatory mouse model, using some examples from our current research. We will focus on neuroinflammation as a potential treatment target for neurodegenerative diseases including multiple sclerosis (MS), Parkinson’s (PD), and Alzheimer’s disease (AD) for these plant-derived, anti-inflammatory molecules and highlight cytokine suppressive anti-inflammatory drugs (CSAIDs) as a better alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) to treat neuroinflammatory disorders.

Autism Spectrum Disorders (ASD) are neuro-developmental pathologies characterized by social communication and interaction deficiency, and repetitive and restricted behaviors. The social motivation network, notably the nucleus accumbens (NAc), is dysfunctional in these disorders. We previously showed that pharmacological treatment facilitating the activity of the mGlu4 glutamate receptor relieves autistic symptoms in the Oprm1 -/- mouse model of autism. Interestingly, we also evidenced that mGlu4 can modulate the activity of the amygdala, a critical brain region for emotional responses and social behavior. Aim: Our hypothesis is mGlu Autism Spectrum Disorders (ASD) are neuro-developmental pathologies characterized by social communication and interaction deficiency, and repetitive and restricted behaviors. The social motivation network, notably the nucleus accumbens (NAc), is dysfunctional in these disorders. We previously showed that pharmacological treatment facilitating the activity of the mGlu4 glutamate receptor relieves autistic symptoms in the Oprm1 -/- mouse model of autism. Interestingly, we also evidenced that mGlu4 can modulate the activity of the amygdala, a critical brain region for emotional responses and social behavior. Aim: Our hypothesis is mGlu4 in the NAc and the basolateral amygdala (BLA) plays a critical role in modulating autism-sensitive symptoms, namely social motivation and stereotyped behaviors. Methods : In order to test this, we performed the knockdown of the gene coding for mGlu4, Grm4 , in the nucleus accumbens or the basolateral amygdala of wild-type mice using bilateral stereotaxic injections of shRNA-expressing AAVs. We tested them in several behavioral tests to evaluate the presence or not of autistic symptoms. In the end, we conducted qRT-PCR analysis in several structures of reward circuit in these same mice. Results: Knocking down (KD) of Grm4 expression in NAc neurons induces autistic-like symptoms such as impaired social interactions and social preference, and impacts gene expression in several brain regions. In contrast, we expect that knocking down Grm4 expression in BLA neurons will elicit modifications in social anxiety levels. Conclusions : These results suggest that mGlu4 receptors expressed in the NAc and BLA neurons play a major role in modulating sociability in mice.4 in the NAc and the basolateral amygdala (BLA) plays a critical role in modulating autism-sensitive symptoms, namely social motivation and stereotyped behaviors. Methods : In order to test this, we performed the knockdown of the gene coding for mGlu4, Grm4 , in the nucleus accumbens or the basolateral amygdala of wild-type mice using bilateral stereotaxic injections of shRNA-expressing AAVs. We tested them in several behavioral tests to evaluate the presence or not of autistic symptoms. In the end, we conducted qRT-PCR analysis in several structures of reward circuit in these same mice. Results: Knocking down (KD) of Grm4 expression in NAc neurons induces autistic-like symptoms such as impaired social interactions and social preference, and impacts gene expression in several brain regions. In contrast, we expect that knocking down Grm4 expression in BLA neurons will elicit modifications in social anxiety levels. Conclusions : These results suggest that mGlu4 receptors expressed in the NAc and BLA neurons play a major role in modulating sociability in mice.

Autism Spectrum Disorders (ASD) are neuro-developmental pathologies characterized by social communication and interaction deficiency, and repetitive and restricted behaviors. The social motivation network, notably the nucleus accumbens (NAc), is dysfunctional in these disorders. We previously showed that pharmacological treatment facilitating the activity of the mGlu4 glutamate receptor relieves autistic symptoms in the Oprm1 -/- mouse model of autism. Interestingly, we also evidenced that mGlu4 can modulate the activity of the amygdala, a critical brain region for emotional responses and social behavior. Aim: Our hypothesis is mGlu4 in the NAc and the basolateral amygdala (BLA) plays a critical role in modulating autism-sensitive symptoms, namely social motivation and stereotyped behaviors. Methods : In order to test this, we performed the knockdown of the gene coding for mGlu4, Grm4 , in the nucleus accumbens or the basolateral amygdala of wild-type mice using bilateral stereotaxic injections of shRNA-expressing AAVs. We tested them in several behavioral tests to evaluate the presence or not of autistic symptoms. Results: Knocking down (KD) of Grm4 expression in NAc neurons induces autistic-like symptoms such as impaired social interactions and social preference Conclusions : These results suggest that mGlu4 receptors expressed in the NAc and BLA neurons play a major role in modulating sociability in mice.