Reduced Alcohol Seeking and Withdrawal Symptoms in Mice Lacking the BDNF Receptor SorCS2

Alcohol use disorder (AUD) is characterized by repetitive and uncontrolled intake of alcohol with severe consequences for affected individuals, their families and society as a whole. Numerous studies have implicated brain-derived neurotrophic factor (BDNF) activity in the neurobiology underlying AUD. The BDNF signaling mechanism is complex and depends on two receptor systems, TrkB and p75NTR, which appear to have opposite effects on alcohol seeking behavior in animal models. We recently discovered that the sortilin-related receptor SorCS2 forms complexes with both TrkB and p75NTR and is important for BDNF activity in the developing and adult CNS. Moreover, the SORCS2 gene was recently identified as the top association signal for severity of alcohol withdrawal symptoms. Hence, we speculated that SorCS2 deficient mice would have an altered response to alcohol. The role of SorCS2 in the acute and adapted response to alcohol was therefore investigated by comparing SorCS2 knockout (Sorcs2−/−) mice to wild type (WT) mice in three paradigms modeling alcohol sensitivity and consumption; alcohol-induced conditioned place preference, two-bottle choice test as well as the behavioral response to alcohol withdrawal. We found that, when compared to the WT mice, (I) Sorcs2−/− mice displayed complete lack of alcohol-induced place preference, (II) when given free choice between water and alcohol, Sorcs2−/− mice consumed less alcohol, and (III) Sorcs2−/− mice showed no handling-induced convulsion in response to alcohol withdrawal following extended alcohol exposure. Taken together, these results show that lack of the alcohol withdrawal risk gene Sorcs2 results in abnormal behavioral response to alcohol in mice. Consequently, SorCS2 may play an important role in the molecular pathways underlying AUD and complications associated with alcohol withdrawal

Ligature-associated bacterial profiles are linked to type 2 diabetes mellitus in a rat model and influenced by antibody treatment against TNF-α or RAGE

There is a bidirectional relationship between periodontal disease (PD) and type 2 diabetes mellitus (T2D). T2D may lead to ecological perturbations in the oral environment, which may facilitate an altered microbiota. However, previous studies have been inconclusive in determining the effect of T2D on oral bacterial profiles. Therefore, we aimed to evaluate the influence of T2D on the ligature‐associated bacterial profile in a diabetic rat model with PD and investigated the impact of blocking inflammatory pathways with antibodies targeting either Tumor Necrosis Factor α (TNF‐α) or the receptor of advanced glycation end‐products (RAGE). A total of 62 Zucker obese rats (45 T2D) and 17 lean (non‐T2D) were divided into 4 treatment groups; lean with PD, obese with PD, obese with PD and anti‐TNF‐α treatment, and obese with PD with anti‐RAGE treatment. Periodontal disease was ligature induced. Ligature‐associated bacterial profiles were analyzed using Human Oral Microbe Identification Microarray (HOMIM). Ligature‐associated bacterial profiles differed between lean and obese rats. Furthermore, treatment with antibodies against TNF‐α or RAGE had an impact on subgingival bacterial profiles. T2D phenotypes are associated with different ligature‐associated bacterial profiles and influenced by treatment with antibodies against TNF‐α or RAGE

Empirical tests of natural selection-based evolutionary accounts of ADHD: a systematic review

ADHD is a prevalent and highly heritable mental disorder associated with significant impairment, morbidity and increased rates of mortality. This combination of high prevalence and high morbidity/mortality seen in ADHD and other mental disorders presents a challenge to natural selection-based models of human evolution. Several hypotheses have been proposed in an attempt to resolve this apparent paradox. The aim of this study was to review the evidence for these hypotheses.We conducted a systematic review of the literature on empirical investigations of natural selection-based evolutionary accounts for ADHD in adherence with the PRISMA guideline. The PubMed, Embase, and PsycINFO databases were screened for relevant publications, by combining search terms covering evolution/selection with search terms covering ADHD.The search identified 790 records. Of these, 15 full-text articles were assessed for eligibility, and three were included in the review. Two of these reported on the evolution of the seven-repeat allele of the ADHD-associated dopamine receptor D4 gene, and one reported on the results of a simulation study of the effect of suggested ADHD-traits on group survival. The authors of the three studies interpreted their findings as favouring the notion that ADHD-traits may have been associated with increased fitness during human evolution. However, we argue that none of the three studies really tap into the core symptoms of ADHD, and that their conclusions therefore lack validity for the disorder.This review indicates that the natural selection-based accounts of ADHD have not been subjected to empirical test and therefore remain hypothetical

The electron density is smooth away from the nuclei

We prove that the electron densities of electronic eigenfunctions of atoms and molecules are smooth away from the nuclei.Comment: 16 page