Adolescent Delta-9-tetrahydrocannabinol induces long-term neuronal disturbances in dorsal vs. ventral hippocampus
De Felice et al reported in Neuropsychopharmacology (2022) how adolescent THC exposure in a rodent model can induce significant morphological disturbances and glutamatergic signaling abnormalities in the hippocampus. The dorsal hippocampus is critical for cognitive and contextual processing, whereas the ventral region is critical for affective and emotional processing. Adolescent THC exposure induces long-lasting memory deficits and anxiety like-behaviors concomitant with a wide range of differential molecular and neuronal abnormalities in dorsal vs. ventral hippocampal regions.
Editors Note: While these data are in rodents, they provide insights into how THC use in adolescents exerts memory deficits and anxiety-like behavior in adulthood by dysregulation of glutamate signaling in the hippocampus. These data converge with data in humans. The bottom line is: use of marijuana in adolescence is not good for brain function, cognition, and behavior in adulthood.
DNA Repair Plays Role in Brain Development, Cancer, and Aging
DNA has several ways of repairing itself. Serious damage, including breaks to both strands of the double helix and problems with replication, prompt a process known as DNA damage repair, or DDR. Researcher Stephen J. Elledge of Harvard Medical School won the 2015 Albert Lasker Basic Medical Research Award for his findings about DDR. He summarized these findings in a September article in the journal JAMA.
DDR occurs because of DNA’s remarkable self-awareness. Through the DDR process, DNA can detect when it has been damaged and prompt the right kind of repair. When damage occurs, DDR allows for the activation of enzymes that can remodel DNA to maintain the integrity of the genome.
When DDR pathways are activated, they can alter more than 1000 different proteins. DDR can affect immune function, blood and bone marrow, viral response, cancer, aging, and brain development.
Mutations in components of the DDR pathway can lead to problems with brain development, including Seckel syndrome (characterized by dwarfism, brain and facial abnormalities, and mental retardation) and ataxia telangiectasia (loss of control of bodily movements along with weakened immune system).
DDR is particularly relevant to cancer, since properly functioning DDR promotes a stable genome. Classic cancer treatments such as radiation and chemotherapy also rely on DDR to prompt cell death.
DDR also plays a role in aging. When we get older or have certain illnesses, telomeres, bits of material at the end of DNA strands that protect the DNA during replication, get shorter. This prompts DDR to engage in tumor prevention measures, either killing off the cells or changing them into what’s called senescent cells. Senescent cells prevent tumors, but their accumulation is associated with chronic inflammation, aging, and age-related diseases.
Editor’s Note: You can protect your telomeres and possibly hold off the age-related effects of DDR. Healthy diet, exercise, meditation, goal setting, and making positive contributions to society all help maintain telomere length. Lithium treatment also directly increases telomere length.
Marijuana May Speed Cortical Loss in Boys at Risk for Schizophrenia
In boys, a decrease in the thickness of the cortex is a part of normal maturation. However, according to a recent study, this process is sped up in boys at high risk for schizophrenia when they use marijuana before the age of 16.
Early use of marijuana has been linked to subsequent development of schizophrenia. Schizophrenia begins about 5 years earlier in males than in females, and the male brain goes through more structural changes during adolescence.
A 2015 article by Tomáš Paus in the journal JAMA Psychiatry incorporated data from three studies, which took place in parts of Canada and England and eight European cities. The studies all included magnetic resonance imaging (MRI) scans of the participants, a measure of their genetic risk of developing schizophrenia, and questions about their past marijuana use. In boys at high risk for schizophrenia based on their genetic profile, cortical thickness dropped more among the ones who used high amounts of marijuana before the age of 16 compared to those who did not.
Paus hypothesizes that the development of schizophrenia is a “two-hit process.” People who develop schizophrenia may have an early risk factor, such as their genetic profile or a problem that occurs in utero, and a later stressor such as drug use in adolescence.
Poverty Impacts Brain Development
In a 2013 study of children by Luby et al. in the Journal of the American Medical Association Pediatrics, poverty in early childhood was associated with smaller white and gray matter in the cortex and with smaller volume of the amygdala and hippocampus when the children reached school age. The effects of poverty on hippocampal volume were mediated by whether the children experienced stressful life events and whether a caregiver was supportive or hostile.
The children were recruited from primary care and day care settings between the ages of three and six, and were studied for five to ten years. They were initially assessed annually for three to six years and information on psychosocial, behavioral, and developmental dimensions were collected. Then the children took part in a magnetic resonance imaging (MRI) scan and continued annual assessments that included information such as whether the children experienced stressful life events.
Previous research has shown that poverty affects children’s psychosocial development and economic success in adulthood. This research shows that poverty also affects brain development. The findings suggest important targets for intervention that could help prevent these developmental deficits.
