Test, rinse, repeat: A review of carryover effects in rodent behavioral assays

10.1016/j.neubiorev.2022.104560NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS13

Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system

Dysregulations in the brain serotonergic system and exposure to environmental stressors have been implicated in the development of major depressive disorder. Here, we investigate the interactions between the stress and serotonergic systems by characterizing the behavioral and biochemical effects of chronic stress applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild stress applied in adulthood did not affect the behaviors and serotonin levels of WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress increased anxiety-and depressive-like behaviors of WT mice, with no detectable behavioral changes in TPH2, KI mice. Biochemically, we found that MS WT mice had reduced brain serotonin levels, which was attributed to increased expression of monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To determine whether a pharmacological stressor, dexamethasone (Dex), will result in similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y cells, and found that Dex treatment resulted in increased MAO A expression levels. We then treated WT mice with Dex for 5 days, either during postnatal days 7-11 or adulthood. Both groups of Dex treated WT mice had reduced basal corticosterone and glucocorticoid receptors expression levels. However, only Dex treatment during PND7-11 resulted in reduced serotonin levels and increased MAO A expression. Just as with MS WT mice, TPH2 expression in PND7-11, Dex-treated WT mice was unaffected. Taken together, our findings suggest that both environmental and pharmacological stressors affect the expression of MAO A, and not TPH2, when applied during the critical postnatal period. This leads to long-lasting perturbations in the serotonergic system, and results in anxiety-and depressive-like behaviors

Commentary on: "Why people see things that are not there: A novel Perception and Attention Deficit model for recurrent complex visual hallucinations" by Believing is Seeing in Schizophrenia: The role of top-down processing

The etiology of visual hallucinations is largely undetermined in schizophrenia. The PAD model partly concurs with what we know about neurocognition in schizophrenia but we need to specify the types of perceptual and attentional abnormalities that are implicated in RCVH. Available data suggest that abnormal attentional control and top-down processing play a larger role than the ventral stream deficits

Cellular Scaling Rules for the Brains of an Extended Number of Primate Species

What are the rules relating the size of the brain and its structures to the number of cells that compose them and their average sizes? We have shown previously that the cerebral cortex, cerebellum and the remaining brain structures increase in size as a linear function of their numbers of neurons and non-neuronal cells across 6 species of primates. Here we describe that the cellular composition of the same brain structures of 5 other primate species, as well as humans, conform to the scaling rules identified previously, and that the updated power functions for the extended sample are similar to those determined earlier. Accounting for phylogenetic relatedness in the combined dataset does not affect the scaling slopes that apply to the cerebral cortex and cerebellum, but alters the slope for the remaining brain structures to a value that is similar to that observed in rodents, which raises the possibility that the neuronal scaling rules for these structures are shared among rodents and primates. The conformity of the new set of primate species to the previous rules strongly suggests that the cellular scaling rules we have identified apply to primates in general, including humans, and not only to particular subgroups of primate species. In contrast, the allometric rules relating body and brain size are highly sensitive to the particular species sampled, suggesting that brain size is neither determined by body size nor together with it, but is rather only loosely correlated with body size

A Preliminary Study on Grip-Induced Nerve Damage Caused by a Soft Pneumatic Elastomeric Gripper

Forceps, clamps, and haemostats are essential surgical tools required for all surgical interventions. While they are widely used to grasp, hold, and manipulate soft tissue, their metallic rigid structure may cause tissue damage due to the potential risk of applying excessive gripping forces. Soft pneumatic surgical grippers fabricated by silicone elastomeric materials with low Young’s modulus may offer a promising solution to minimize this unintentional damage due to their inherent excellent compliance and compressibility. The goal of this work is to evaluate and compare the grip-induced nerve damage caused by the soft pneumatic elastomeric gripper and conventional haemostats during surgical manipulation. Twenty-four Wistar rats (male, seven weeks) are subjected to sciatic nerve compression (right hind limb) using the soft pneumatic elastomer gripper and haemostats. A histopathological analysis is conducted at different time-points (Day 0, Day 3, Day 7 and Day 13) after the nerve compression to examine the morphological tissue changes between the rats in the ‘soft gripper’ group and the ‘haemostats’ group. A free walking analysis is also performed to examine the walking function of the rats after recovery from different time points. Comparing the rigid haemostats and soft gripper groups, there is a visible difference in the degree of axonal vacuolar degeneration between the groups, which could suggest the presence of substantial nerve damage in the ‘haemostats’ group. The rats in the haemostats group exhibited reduced right hind paw pressure and paw size after the nerve compression. It shows that the rats tend not to exert more force on the affected right hind limb in the haemostats group compared to the soft gripper group. In addition, the stance duration was reduced in the injured right hind limb compared to the normal left hind limb in the haemostats group. These observations show that the soft pneumatic surgical gripper made of silicone elastomeric materials might reduce the severity of grip-induced damage by providing a safe compliant grip compared to the conventional haemostats. The soft pneumatic elastomer gripper could complement the current surgical gripping tool in delicate tissue manipulation

Pregnenolone normalizes the episodic memory deficits in DAT KO mice.

<p>WT and DAT KO mice were injected (s.c.) with vehicle or 60 mg/kg Preg for 14 consecutive days and were tested in the novel object recognition (A) and social transmission of food preference (B) tests for short-term (STM), long-term (LTM), and remote memory. Number of contacts with the novel and familiar objects in the novel object recognition test (C) and the amount of food consumed in the social transmission of food preference test (D) were analysed. For the novel object recognition test, N = 9–12, and for the social transmission of food preference test, N = 9–11.</p

Effects of pregnenolone, haloperidol and clozapine on activities of WT and DAT KO mice in the open field.

<p>Baseline activities were monitored over 30 min, the mice were injected (i.p.) with vehicle, or 30 or 60 mg/kg pregnenolone (Preg) and returned immediately to the open field for 2 h. Cumulative distance traveled (A), vertical activity (B), and stereotypical activities (B) are shown. (D–F) Cumulative post-injection activities after WT and DAT KO mice were administered (i.p.) vehicle, 0.2 mg/kg haloperidol (HAL), 2.0 mg/kg clozapine (CLZ), or 60 mg/kg Preg, and monitored for locomotor (D), rearing (E), and stereotypical (F) activities. N = 9–15 mice/genotype/treatment condition, ^a<i>p</i><0.05, WT-Veh versus KO-Veh; ^b<i>p</i><0.05, within groups versus Veh; ^c<i>p</i><0.05, within groups HAL or CLZ versus Preg60.</p

Pregnenolone rescues PPI in DAT KO mice.

<p>WT and DAT KO mice were injected (i.p.) with vehicle, or 30, or 60 mg/kg Preg and were tested in PPI 5 min later. (A) Amplitude of the startle responses of WT and DAT KO mice. (B) PPI levels of WT and DAT KO mice. White bars represent WT and grey bars represent DAT KO performance. N = 9–14 mice/genotype/treatment condition; ^a<i>p</i><0.05, WT-Veh versus KO-Veh; ^b<i>p</i><0.05, WT-Preg30 versus KO-Preg30; ^c<i>p</i><0.05, within groups versus Veh; ^d<i>p</i><0.05, within groups Preg30 versus Preg60.</p