Postdoc Wins Professional Development Award

Murlanova works in the lab of Mikhail V. Pletnikov, MD, PhD, professor and chair of physiology and biophysics.

The major focus of her research is on uncovering roles of non-neuronal cells of the brain — for example, astrocytes — in the mechanisms of neurodevelopmental disorders.

Astrocytes have close spatial relationship with neurons and regulate various neuronal functions.

“However, we know little about astrocytes’ contribution of human mental or behavioral disorders,” Murlanova says. “My preclinical project seeks to investigate if and how astrocytes respond to adverse environmental factors such as viral infection during pregnancy and/or adolescent exposure to cannabis.”

“We hope that targeting abnormal changes in astrocytes could lead to the development of new treatment of mental disorders,” she notes.

As a TPDA recipient, Murlanova received complimentary registration to Neuroscience 2021, the fully virtual SfN annual meeting, which was held Nov. 8-11.

At the meeting, she presented a research posted titled “Long-Term Effects of Adolescent THC Exposure: Role of Prenatal Environment.”

“In my poster I showed how environmental insult taking place in early brain development (prenatally) can lead to long-lasting detrimental effects of adolescent cannabis,” Murlanvoa says.

Cannabis is the most-used illicit drug worldwide, particularly among adolescents. During adolescence important changes take place in the structure and workings of the brain, which renders the adolescent brain especially vulnerable to cannabis.

Cannabis use during adolescence can result in persistent deficits in attention, memory and other cognitive functions. Adolescent cannabis use is also linked to an increased risk for adult psychiatric disorders, including psychoses, depression, anxiety and substance use disorders.

“Still, not all cannabis users develop long-term behavioral impairments,” Murlanova notes. “I was wondering if viral infections during pregnancy can increase susceptibility to adverse effects of cannabis in teenagers.”

She injected pregnant mice with a viral-like compound that mimics viral infection by inducing in these mice a strong immune response and an associated release of cytokines, much like the cytokine storm produced by COVID-19 infection.

Pro-inflammatory cytokines pass on to the fetuses and exert various pathological effects on the fetal brain, including abnormal maturation of the brain dopamine system that has been associated with the onset of major neuropsychiatric disorders in late adolescence.

“We expected to see environment-environment interaction between viral infection in utero and adolescent cannabis to impair the maturation of the dopamine system, leading to behavioral and cognitive dysfunction in adult offspring,” Murlanova says.

The results showed that mice that were exposed both to viral infection prenatally and THC during adolescence showed increased exploratory and repetitive behavior, as well as exaggerated response to amphetamine, a psychostimulant, she notes.

“Importantly, neither viral infection nor cannabis had any significant effects on mice when presented as separate insults, suggesting the importance of environment-environment interplay to produce adult psychopathology,” Murlanova adds.

Murlanova says a better understanding of what factors could exacerbate potential adverse effects of cannabis use during adolescence will help researchers develop preventive and treatment strategies, including identifying susceptible individuals.

“Our lab previously showed that cannabis exposure increases inflammation in astrocytes, and this inflammatory response was significantly increased in mice engineered to express a genetic risk factor associated with major psychiatric disorders,” she says.

“We were able to prevent adverse consequences of cannabis-induced inflammation in susceptible mice by treating them with the nonsteroid anti-inflammatory drug,” Murlanova says. “If these results turn out to be applicable to people, they suggest that anti-inflammatory treatments could prevent long-term consequences of marijuana.”

Pletnikov and Yan Jouroukhin, PhD, a former member of the Pletnikov lab, were co-authors on the poster.

Murlanova says she felt inspired by winning the TPDA.

“It is so great when your research is recognized, and it inspires you to keep going and be more creative,” she says.

“The Society for Neuroscience meeting is the perfect opportunity to network with other like-minded researchers and there were so many amazing posters and a variety of information that keeps us abreast of the latest advancements in the field of neuroscience.”

“Moreover, my project requires the application of novel technologies, and the Society for Neuroscience meeting is the best chance to expand knowledge and expertise to modern approaches in neuroscience,” Murlanova says.