This suggests multiple critical period windows in postnatal life wherein disruption of serotonergic neurotransmission could have opposing effects on mood, paralleled by differential molecular, cellular and bioenergetic consequences

It is difficulty to clear extrapolate the temporal windows tested here in rodents to precise equivalents in humans, but points to the possibility that exposure to SSRIs in distinct time windows of childhood and adolescence may exert long-lasting consequences.

This all adds to a body of literature that indicates very long-term effects across the life-span that emerge when serotonergic neurotransmission is disrupted in developmental temporal windows, and also highlights that timing of perturbation is key.

This phenotype is noted in male, but not female, rats and underscores the importance to looking carefully at long-term effects of early perturbations in both sexes.

Early exposure to Prozac evokes diametrically opposing effects on mood behavior, global gene expression, dendritic architecture and mitochondrial function in the prefrontal cortex which is long-lasting and persists well into adulthood.

Work from former graduate student @utkarshaghai ably assisted by several labmates - examining the persistent marks associated with postnatal and juvenile exposure to Prozac

A big shout out to Sashaina Fanibunda, Kowshik Kukkemane, Utkarsha Ghai and our collaborators, Ullas Kolthur and Lal Hingorani - and of course raising a toast to my Dad, Dr. Ashok Vaidya - who remains an inspiration to me always.

A modern medicine mindset of a clear preference for single molecule therapeutics, has been widened to consider benefits of multi-targeted therapy - opening the path to use modern tools to investigate both the veracity, and mechanisms, of insights from indigenous knowledge systems.

In the context of plant and fungi-derived natural products with psychoactive effects, there has been a recent resurgence of interest in their therapeutic utility to treat neuropsychiatric and neurodegenerative disorders - for eg. serotonergic psychedelics

In his words "Reverse pharmacology will have to maintain dynamism, flexibility, and a progressive approach to adopt and assimilate relevant scientific and technological advancements along with the due cognition of a rich, untapped heritage"

My father continued to stay deeply engaged with this work from its conception uptil submission of the manuscript - there has been nothing more precious to me than this opportunity to collaborate with him - on a reverse pharmacology approach that he championed his whole life.

Our findings suggest that the stress resilience boosting effects empirically and clinically observed with Aswagandha root extract may involve the mitochondrial and bioenergetic actions of withania somnifera, mediated via WithanolideA and WithanosideIV through recruiting BDNF-SIRT1 signaling.

Inspired by 'reverse pharmacology' which capitalizes on transdisciplinary insights from indigenous knowledge systems - we set out to ask if mitochondria and bioenergetics might be a key target in neurons - which could contribute to the putative neuroprotective effects of Ashwaganda

In our study led by Sashaina Fanibunda, a collaboration between TIFR and MRC-KHS uncovered the potent effects of Withania somnifera on mitochondrial biogenesis and function in cortical neurons - driven via BDNF and SIRT1 signaling.

Many drugs are derived from the knowledge domain of natural products- with famous examples including the aspirin, digitoxin, taxol, quinine and artemesinin - highlighting the importance of continuing to explore plant-derived phytoactives using state of the art modern tools.

What a started as conversations between our team with my father, the late Prof. Ashok Vaidya, matured into this story, which has a special place in my heart as it is dedicated to his memory. link.springer.com/article/10.1...