Papers by Arathy Ramachandran
Alzheimer's & Dementia, 2020
Background: Imaging and neuropathological studies have revealed the entorhinal cortex (EC) and hi... more Background: Imaging and neuropathological studies have revealed the entorhinal cortex (EC) and hippocampus (HP) circuitry to be affected early on during Alzheimer's disease (AD) progression. Changes in the EC-HP circuitry also correlate with the episodic memory deficits that have been reported in AD. Using bulk RNA sequencing, we stud
Alzheimer's & Dementia, 2020
Women and men are differently affected in Alzheimer’s disease (AD). However, the factors that con... more Women and men are differently affected in Alzheimer’s disease (AD). However, the factors that contribute to this differential AD epidemiology are not well understood. We, therefore, examined how gene expression changes could work differently in females and males in the APPswe/PS1ΔE9 (APP/PS1) mouse model of AD using RNA sequencing (RNA‐seq).

Alzheimer's & Dementia, 2018
insulin, lipidomics and, circulating cytokines and chemokines. Hippocampal RNA-Seq and brain mito... more insulin, lipidomics and, circulating cytokines and chemokines. Hippocampal RNA-Seq and brain mitochondrial function assessment was conducted in the rats that underwent FDG-microPET/CT. Magnetic resonance imaging (MRI) using 3-dimensional high resolution T2-weighted sequence and diffusion-weighted MRI was also carried out. Regional brain volume assessment using atlasbased analysis and white matter integrity assessment using diffusion parameters related tissue microstructure are currently underway. Results: Longitudinal analyses indicate female and male APOE-ε4 rats had significantly higher triglyceride and ketone body plasma levels. Female APOE-ε4 underwent an age-related decline in insulin levels and increase in ketone body levels. At 16m, APOE-ε4 males had higher brain glucose uptake than APOE-ε4 females. Age did not affect the brain glucose uptake in APOE-ε4 males. In comparison to WT-females, APOE-ε4 females exhibited significant decline in brain glucose uptake at 12-13m, after reproductive senescence. Analyses correlating the transcriptional profile with brain glucose uptake and mitochondrial function are underway. Quantitative assessment of regional brain volume and, correlation with inflammatory and metabolic biomarkers are also underway. Conclusions:Aging did not affect brain glucose uptake in male APOE-ε4 rats, while female APOE-ε4 rats underwent a significant decline following menopausal transition. This longitudinal study demonstrates that APOE-ε4 in combination with endocrine transition states worsens the metabolic trajectory of the aging female brain. Outcomes of this study will contribute to identifying optimal intervention windows for APOE-ε4 carriers and peripheral markers predictive of neurological decline. Supported by NIA-P01AG026572; Alzheimer’s Association: SAGA17-419459; Arizona Alzheimer’s Consortium to RDB.

Antioxidants & redox signaling, Jan 6, 2017
Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease... more Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear if ROS contributes to synaptic dysfunction seen in AD pathogenesis and therefore, we examined if altered redox signaling could contribute to synaptic deficits in AD. Activity-dependent but not basal translation was impaired in synaptoneurosomes from 1 month old presymptomatic APPSwe/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (9-10 months). ROS generationleads tooxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mTOR signaling leading to deficiency in activity dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from post-mortem AD brains. Loss of activity dependent protein translation occurs presymptomatically early in thepathogen...

Insectes Sociaux, 2015
Sex pheromones are vital in communication between individuals belonging to opposite sexes and for... more Sex pheromones are vital in communication between individuals belonging to opposite sexes and form an integral part of the reproductive biology of various species. Among insects, sexual dimorphism in CHCs has been reported from diverse taxa spanning seven different orders, and thereby CHCs have been implicated as sex pheromones. Because males and females of the primitively eusocial wasp Ropalidia marginata touch each other with their antennae during mating, before engaging in sperm transfer, a sex pheromone that is perceived via contact chemosensation through the antennae can possibly exist in this species. Since CHCs have been implied as sex pheromones in various insects (including hymenopterans), and since sexual dimorphism of CHCs should be an obligatory prerequisite for them to act as sex pheromones, we investigated whether males and females of R. marginata differ in their CHC profiles. We found only nonvolatile CHCs, and our results show absence of sexual dimorphism in CHCs, suggesting that CHCs do not function as sex pheromone in this species. A behavioral assay failed to show presence of mate attraction at a distance, thereby showing the absence of volatile long-distance mate attraction cues (that may originate from sources other than and in addition to CHCs).

PLOS Pathogens
Cerebral malaria (CM) is one of the leading causes of death due to malaria. It is characterised b... more Cerebral malaria (CM) is one of the leading causes of death due to malaria. It is characterised by coma, presence of asexual parasites in blood smear, and absence of any other reason that can cause encephalopathy. The fatality rate for CM is high, and those who survive CM often experience long-term sequelae, including cognitive and motor dysfunctions. It is unclear how parasites sequestered in the lumen of endothelial cells of the blood–brain barrier (BBB), and localised breakdown of BBB can manifest gross physiological changes across the brain. The pathological changes associated with CM are mainly due to the dysregulation of inflammatory and coagulation pathways. Other factors like host and parasite genetics, transmission intensity, and the host’s immune status are likely to play a role in the development and progression of CM. This work focuses on the pathological mechanisms underlying CM. Insights from humans, mice, and in vitro studies have been summarised to present a cohesive...
Alzheimer's & Dementia, 2019

"Nestmate discrimination plays an important role in preserving the integrity of social insect col... more "Nestmate discrimination plays an important role in preserving the integrity of social insect colonies. It is
known to occur in the primitively eusocial wasp Ropalidia marginata in which non-nestmate conspecifics
are not allowed to come near a nest. However, newly eclosed females are accepted in foreign colonies,
suggesting that such individuals may not express the cues that permit differentiation between nestmates
and non-nestmates. As cuticular hydrocarbons (CHCs) have been implicated as chemosensory cues used
in nestmate recognition in other species, we investigated, using bioassays and chemical analyses,
whether CHCs can play a role in nestmate recognition in R. marginata. We found that individuals can be
differentiated according to colony membership using their CHC profiles, suggesting a role of CHCs in
nestmate discrimination. Non-nestmate CHCs of adult females received more aggression than nestmate
CHCs, thereby showing that CHCs are used as cues for nestmate recognition. Contrarily, and as expected,
CHCs of newly eclosed females were not discriminated against when presented to a foreign colony.
Behavioural sequence analysis revealed the behavioural mechanism involved in sensing nestmate
recognition cues.We also found that newly eclosed females had a different CHC profile from that of adult
females, thereby providing an explanation for why young females are accepted in foreign colonies."

Sex pheromones are vital in communication
between individuals belonging to opposite sexes and for... more Sex pheromones are vital in communication
between individuals belonging to opposite sexes and form
an integral part of the reproductive biology of various spe-
cies. Among insects, sexual dimorphism in CHCs has been
reported from diverse taxa spanning seven different orders,
and thereby CHCs have been implicated as sex pheromones.
Because males and females of the primitively eusocial wasp
Ropalidia marginata touch each other with their antennae
during mating, before engaging in sperm transfer, a sex
pheromone that is perceived via contact chemosensation
through the antennae can possibly exist in this species. Since
CHCs have been implied as sex pheromones in various in-
sects (including hymenopterans), and since sexual
dimorphism of CHCs should be an obligatory prerequisite
for them to act as sex pheromones, we investigated whether
males and females of R. marginata differ in their CHC profiles. We found only nonvolatile CHCs, and our results
show absence of sexual dimorphism in CHCs, suggesting
that CHCs do not function as sex pheromone in this species.
A behavioral assay failed to show presence of mate attrac-
tion at a distance, thereby showing the absence of volatile
long-distance mate attraction cues (that may originate from
sources other than and in addition to CHCs).
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Papers by Arathy Ramachandran
known to occur in the primitively eusocial wasp Ropalidia marginata in which non-nestmate conspecifics
are not allowed to come near a nest. However, newly eclosed females are accepted in foreign colonies,
suggesting that such individuals may not express the cues that permit differentiation between nestmates
and non-nestmates. As cuticular hydrocarbons (CHCs) have been implicated as chemosensory cues used
in nestmate recognition in other species, we investigated, using bioassays and chemical analyses,
whether CHCs can play a role in nestmate recognition in R. marginata. We found that individuals can be
differentiated according to colony membership using their CHC profiles, suggesting a role of CHCs in
nestmate discrimination. Non-nestmate CHCs of adult females received more aggression than nestmate
CHCs, thereby showing that CHCs are used as cues for nestmate recognition. Contrarily, and as expected,
CHCs of newly eclosed females were not discriminated against when presented to a foreign colony.
Behavioural sequence analysis revealed the behavioural mechanism involved in sensing nestmate
recognition cues.We also found that newly eclosed females had a different CHC profile from that of adult
females, thereby providing an explanation for why young females are accepted in foreign colonies."
between individuals belonging to opposite sexes and form
an integral part of the reproductive biology of various spe-
cies. Among insects, sexual dimorphism in CHCs has been
reported from diverse taxa spanning seven different orders,
and thereby CHCs have been implicated as sex pheromones.
Because males and females of the primitively eusocial wasp
Ropalidia marginata touch each other with their antennae
during mating, before engaging in sperm transfer, a sex
pheromone that is perceived via contact chemosensation
through the antennae can possibly exist in this species. Since
CHCs have been implied as sex pheromones in various in-
sects (including hymenopterans), and since sexual
dimorphism of CHCs should be an obligatory prerequisite
for them to act as sex pheromones, we investigated whether
males and females of R. marginata differ in their CHC profiles. We found only nonvolatile CHCs, and our results
show absence of sexual dimorphism in CHCs, suggesting
that CHCs do not function as sex pheromone in this species.
A behavioral assay failed to show presence of mate attrac-
tion at a distance, thereby showing the absence of volatile
long-distance mate attraction cues (that may originate from
sources other than and in addition to CHCs).
known to occur in the primitively eusocial wasp Ropalidia marginata in which non-nestmate conspecifics
are not allowed to come near a nest. However, newly eclosed females are accepted in foreign colonies,
suggesting that such individuals may not express the cues that permit differentiation between nestmates
and non-nestmates. As cuticular hydrocarbons (CHCs) have been implicated as chemosensory cues used
in nestmate recognition in other species, we investigated, using bioassays and chemical analyses,
whether CHCs can play a role in nestmate recognition in R. marginata. We found that individuals can be
differentiated according to colony membership using their CHC profiles, suggesting a role of CHCs in
nestmate discrimination. Non-nestmate CHCs of adult females received more aggression than nestmate
CHCs, thereby showing that CHCs are used as cues for nestmate recognition. Contrarily, and as expected,
CHCs of newly eclosed females were not discriminated against when presented to a foreign colony.
Behavioural sequence analysis revealed the behavioural mechanism involved in sensing nestmate
recognition cues.We also found that newly eclosed females had a different CHC profile from that of adult
females, thereby providing an explanation for why young females are accepted in foreign colonies."
between individuals belonging to opposite sexes and form
an integral part of the reproductive biology of various spe-
cies. Among insects, sexual dimorphism in CHCs has been
reported from diverse taxa spanning seven different orders,
and thereby CHCs have been implicated as sex pheromones.
Because males and females of the primitively eusocial wasp
Ropalidia marginata touch each other with their antennae
during mating, before engaging in sperm transfer, a sex
pheromone that is perceived via contact chemosensation
through the antennae can possibly exist in this species. Since
CHCs have been implied as sex pheromones in various in-
sects (including hymenopterans), and since sexual
dimorphism of CHCs should be an obligatory prerequisite
for them to act as sex pheromones, we investigated whether
males and females of R. marginata differ in their CHC profiles. We found only nonvolatile CHCs, and our results
show absence of sexual dimorphism in CHCs, suggesting
that CHCs do not function as sex pheromone in this species.
A behavioral assay failed to show presence of mate attrac-
tion at a distance, thereby showing the absence of volatile
long-distance mate attraction cues (that may originate from
sources other than and in addition to CHCs).