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Cannabis and mental health
Published in David B Cooper, Practice in Mental Health—Substance Use, 2018
Why do people with mental illness persist in using cannabis and why do they appear to prefer the most potent forms? At present, no clear-cut answers emerge. It is clear that the endogenous cannabinoid system is involved in reward/reinforcement/addiction, as well as the process of psychosis. This is also the case for the neuromodulator, dopamine. The next few years are likely to confirm the importance of cannabinoids in the process of addiction, and for some a cannabinoid hypothesis may come to rival the more long-standing dopamine hypothesis. But this is to misunderstand the neurobiology. The cannabinoid and dopamine systems are intimately linked throughout the reward pathways, thus both systems are important. Teasing out the detail will rely on modern molecular neuroscience, for example conditional gene knockout technology, in vivo voltammetry and electrophysiology. The prospect is that as we learn more about the neurological underpinnings of addiction, we will also learn more about the process of psychosis.
Expression Profile Analysis of Brain Aging
Published in David R. Riddle, Brain Aging, 2007
Because the mechanisms underlying the aging process are likely to be quite complex, there is a high probability that expression profiles within the CNS will reveal a hierarchy of mosaics at the regional, laminar, nuclear, and cellular levels. There is currently no widely accepted biomarker for aging. A goal of modern molecular neuroscience is to develop reliable molecular fingerprints for age-related research similar to the translational design of cancer-related paradigms [3, 200, 201]. Aging is likely a polygenic phenomenon, and microarray analysis can help to identify transcripts contributing to longer life and define genes contributing positively or adversely to the aging process. The application of microarray technology has generated significant interest across several disciplines and spans a multiplicity of biological systems. However, the brain remains a difficult organ to study, in part due to the regional and cellular heterogeneity of brain regions and cell types [6, 21]. Thus, a combination of single cell/population cell analysis is a highly desirable paradigm whereby expression profiles of single populations of neuronal and nonneuronal subtypes can be analyzed and compared under normal and pathological conditions [15, 26, 153, 154, 175]. The transcript profile in a homogeneous population of neurons may be more informative than patterns derived from whole brain or regional tissue homogenates [6], as each neuronal subtype is likely to have a unique molecular signature in normative and diseased states. The next level of understanding of cellular and molecular mechanisms underlying the neurobiology of aging, and of associated pathophysiology of late-onset progressive neurodegenerative disorders such as AD, ALS, and PD, lies in the ability to combine these aforementioned technologies with appropriate models to recapitulate the structure and connectivity of these systems in vivo and in vitro. As our ability to refine expression profiling paradigms increases, the development of pharmacotherapeutic agents and delivery systems that are more effective, as well as selective or potentially specific for individual cell types, becomes more realistic. An important caveat for microarray studies and functional genomics evaluations as a whole is that changes in mRNA levels may not always result in concomitant and/or coincident alterations in respective protein levels. Notwithstanding this issue, mosaics that are generated using expression profiling methods in age-related studies are an exciting and important contributor to the current repertoire of tools available to understand the complex mechanisms that underlie cellular and molecular programs of senescence.
Combinatorial therapeutic strategies for enhanced delivery of therapeutics to brain cancer cells through nanocarriers: current trends and future perspectives
Published in Drug Delivery, 2022
Xiande Wang, Cheng Wu, Shiming Liu, Deqing Peng
Advances in molecular neuroscience and nanocarrier-based drug delivery platforms have changed the deployment of nanotechnology-based techniques for the improved treatment of metastatic brain cancers. Nanocarrier-based drug delivery platforms are projected to reach new heights in the next years, bringing about significant improvements in oncology research. As the five-year survival rate of brain cancer patients remains low, successful clinical translation of nanocarriers is critical. Nano drug delivery systems for the brain must be well-characterized, in terms of safety, biocompatibility, biodegradability, and, of course, must be intelligent in order to function well in in vivo conditions. However, it must be target-specific, i.e., it must be concentrated in brain tissue and successfully traverse the BBB while avoiding off-target drug release in order to have a maximum therapeutic impact with minimal side effects.
The foraging gene as a modulator of division of labour in social insects
Published in Journal of Neurogenetics, 2021
Christophe Lucas, Yehuda Ben-Shahar
However, modern neuroscience research is now largely framed in the context of causation and mechanism (Tinbergen question #4). Consequently, the diversity of animal species used for basic neurogenetic research has, historically, been reduced to just a few genetically tractable species that have sequenced genomes, including the roundworm Caenorhabditis elegans (Bargmann, 1998), the fruit fly Drosophila melanogaster (Bellen, Tong, & Tsuda, 2010), the zebrafish Danio rerio (Stewart, Braubach, Spitsbergen, Gerlai, & Kalueff, 2014), and the laboratory mouse Mus musculus (Lehner, 2013). While there is no doubt that these models have been instrumental in the phenomenal progress made in cellular and molecular neuroscience over the past three decades, the decline in model diversity is clearly an unfortunate side effect, and has negatively impacted our ability to understand behaviour in ecologically and evolutionary relevant contexts (Fitzpatrick et al., 2005; Walton, Sheehan, & Toth, 2020).
Lipid-based nanoformulations in the treatment of neurological disorders
Published in Drug Metabolism Reviews, 2020
Faheem Hyder Pottoo, Shrestha Sharma, Md. Noushad Javed, Md. Abul Barkat, Md. Sabir Alam, Mohd. Javed Naim, Ozair Alam, Mohammad Azam Ansari, George E. Barreto, Ghulam Md. Ashraf
Neurological disorders affect the brain, spine, and the nerves that connect them. There are more than 600 types of such disorders, some of which include epilepsy, Parkinson’s disease (PD), ischemic stroke, and multiple sclerosis. In 2015, central nervous system (CNS) disorders were classified as the foremost basis of disability-adjusted life years (DALYs) (250.7 [95% uncertainty interval (UI) 229.1–274.7] million, consisting 10.2% of global DALYs) and are second leading cause of global deaths (9.4 [9.1–9.7] million, consisting 16.8% of global deaths). The total number of persons dying from CNS disorders between 1990 and 2015 had increased up to 36.7%, while DALYs increased up to 7.4% (GBD 2015 Neurological Disorders Collaborator Group 2017). The origin and pathogenesis underlying these disorders are improperly understood. However, in the past few decades, the applications of molecular neuroscience have enabled the scientists to predict connecting links between neurological disorders, and that overlapping pathogenic mechanisms were reported for these disorders (Hardy 1999; Nigar et al. 2016). Unfortunately, current treatment strategies are built on alleviating the signs and symptoms without mitigating the original pathological anomaly (Chen and Pan 2015). Further, the treatment of neurological disorders is challenged by blood–brain barrier (BBB), the web of tightly joined endothelial cells in the brain capillaries. The BBB does not allow the entrance of larger molecules or highly hydrophilic drugs (log P < 1) inside the brain (Su and Sinko 2006).