Vanillin-induced amelioration of depression-like behaviors in rats by modulating monoamine neurotransmitters in the brain.

Olfaction plays an important role in emotions in our daily life. Pleasant odors are known to evoke positive emotions, inducing relaxation and calmness. The beneficial effects of vanillin on depressive model rats were investigated using a combination of behavioral assessments and neurotransmitter measurements. Before and after chronic stress condition (or olfactory bulbectomy), and at the end of vanillin or fluoxetine treatment, body weight, immobility time on the forced swimming test and sucrose consumption in the sucrose consumption test were measured. Changes in these assessments revealed the characteristic phenotypes of depression in rats. Neurotransmitters were measured using ultrahigh-performance liquid chromatography. Our results indicated that vanillin could alleviate depressive symptoms in the rat model of chronic depression via the olfactory pathway. Preliminary analysis of the monoamine neurotransmitters revealed that vanillin elevated both serotonin and dopamine levels in brain tissue. These results provide important mechanistic insights into the protective effect of vanillin against chronic depressive disorder via olfactory pathway. This suggests that vanillin may be a potential pharmacological agent for the treatment of major depressive disorder.

Neuroprotective effects of heptapeptide mystixin.

Neuroprotective effects of heptapeptide mystixin were studied on the neurons of the olfactory cortex in cultured slices of rat brain. Repeated applications of mystixin in doses of 100 mg/ml on brain slices rapidly reduced the amplitudes of AMPA and NMDA receptor-dependent processes. The effects were reversible and activities of these processes partly restored after washout. The peptide in a dose of 250 mg/ml suppressed epileptic discharges induced by chemical convulsive agent pentylenetetrazole. Thus, heptapeptide mystixin exhibited significant neuroprotective properties.

[Protective and antiedema effect of heat shock HSP70 protein in hemorrhagic stroke model in vitro].

An in vitro model of hemorrhagic stroke in live olfactory cortex slices under long-term influence of autoblood has been used and the development of edema in the samples has been studied with simultaneous monitoring of bioelectric activity of the nervous cells. Protection of the nervous cells in the olfactory cortex slices of the spontaneously hypertensive (SHR) rats from consequences of the hemorrhagic stroke was achieved by incubating brain slices for 20 min in glass vials with 1 ml of incubation solution containing heat shock protein HSP70 at a concentration of 10 mg/ml. Then the incubation medium was replaced by 3 ml of autoblood, the action of which on the nervous cells modeled the hemorrhagic stroke. After 360-min incubation in autoblood, the slices were extracted, placed in a perfusion chamber, and washed from autoblood in a flow of pure incubation solution. Then the amplitudes of separate components of the focal potentials (FPs) evoked by electrostimulation of the slices were measured and their changes analyzed. A comparison of the FP amplitudes after the action of HSP70 and autoblood to those in control group of slices showed the degree of injury and the possibility of recovery. The antiedema effects of HSP70 on the hemorrhagic stroke model was evaluated by weighing brain slices with and without the preincubation with protein, and after the subsequent exposure in autoblood. The slices were weighed on a torsion balance. The difference in weights before and after the exposure in autoblood characterized the extent of swelling and edema development in brain slices. It was established that HSP70 produced a pronounced protective antiedema effect on the slices kept in autoblood.

Women with a history of childhood maltreatment exhibit more activation in association areas following non-traumatic olfactory stimuli: a fMRI study.

BACKGROUND: The aim of this study was investigating how women with a history of childhood maltreatment (CM) process non-threatening and non-trauma related olfactory stimuli. The focus on olfactory perception is based on the overlap of brain areas often proposed to be affected in CM patients and the projection areas of the olfactory system, including the amygdala, orbitofrontal cortex, insula and hippocampus. METHODS: Twelve women with CM and 10 controls participated in the study. All participants were, or have been, patients in a psychosomatic clinic. Participants underwent a fMRI investigation during olfactory stimulation with a neutral (coffee) and a pleasant (peach) odor. Furthermore, odor threshold and odor identification (Sniffin' Sticks) were tested. PRINCIPAL FINDINGS: Both groups showed normal activation in the olfactory projection areas. However, in the CM-group we found additionally enhanced activation in multiple, mainly neocortical, areas that are part of those involved in associative networks. These include the precentral frontal lobe, inferior and middle frontal structures, posterior parietal lobe, occipital lobe, and the posterior cingulate cortex. CONCLUSIONS: The results indicate that in this group of patients, CM was associated with an altered processing of olfactory stimuli, but not development of a functional olfactory deficit. This complements other studies on CM insofar as we found the observed pattern of enhanced activation in associative and emotional regions even following non-traumatic olfactory cues.

Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity.

The Trpc2 gene codes for an ion channel found in the vomeronasal organ (VNO). Studies using the Trpc2(-/-) (KO) mouse have exploited the gene's role in signal transduction to explore the VNO's role in pheromonally mediated behaviors. To date, no study has evaluated the impact of the Trpc2 gene on activity within the brain. In this study, we examine the gene's effect on brain regions governing maternal aggression. We intruder-tested lactating dams and then quantified Fos immunoreactivity (Fos-IR) in the vomeronasal amygdala, hypothalamus, olfactory regions and accessory olfactory bulb (AOB). Our data confirm previous reports that loss of the Trpc2 gene severely diminishes maternal aggression. We also show that deletion of the gene results in differential hypotrophy of the glomerular layer (GlA) of the AOB, with the anterior portion the GlA resembling that of wild-type mice, and the posterior portion reduced or absent. This anatomy is suggestive of residual functioning in the apical VNO of these animals. Our Fos study describes an impact of the deletion on a network of 21 brain regions involved in emotion, aggression and olfaction, suggesting that signals from the VNO mediate activity throughout the brain. Home-cage observations of KO dams show specific deficits in nest-building, suggesting a role for pup pheromones in inducing and maintaining pup-directed maternal behaviors as well as maternal aggression.

Contribution of gustation to the palatability of linoleic acid.

We investigated the palatability of a low concentration of linoleic acid (LA) in short-term two-bottle choice tests and licking tests. To examine the contribution of gustation, mice were rendered anosmic with olfactory nerve transection surgery and test solutions were prepared using mineral oil (saturated long-chain hydrocarbon) to minimize textural effects. In the two-bottle choice tests between various pairs of different concentrations of corn oil and LA, both anosmic and the sham-operated mice constantly preferred a higher concentration of corn oil and LA. In the licking tests, the initial licking rate for 1% LA was higher than that for mineral oil in anosmic mice. In accordance with the results of the two-bottle choice test, the initial licking rate for corn oil and LA increased in a concentration-dependent manner in both anosmic and sham-operated mice in the licking test, and reached its peak at 100% corn oil and 1% LA. A preference comparison between 1% LA and 100% corn oil showed that anosmic mice preferred 1% LA over 100% corn oil. These results suggest that mice could recognize dietary fat and fatty acid solutions in the oral cavity without any olfactory or textural cues and the fatty acid recognition on their tongues might provide a pivotal cue to how dietary fat is recognized in the oral cavity.

Odor abnormalities caused by bilateral thalamic infarction.

Odor is the only sensation thought to be unrelated to the thalamus. However, accumulating evidence suggests that the dorsomedial nucleus (DM) of the thalamus is associated with odor. Although the thalamus is prone to ischemia, only a single patient with bilateral DM infarctions was reported to have odor abnormalities. We describe a second such patient with infarctions involving the left DM and the right ventral posterior nucleus and ventral lateral nucleus, nuclei adjacent to the DM, associated with transient edema. In contrast to the previous case, our patient had transient odor abnormality. These observations suggested that direct and/or indirect bilateral involvement of the DM might be associated with odor abnormalities in patients with thalamic infarction.

Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures.

Low-frequency stimulation (LFS) is an antiepileptic and antiepileptogenic electrical stimulation. In this study the effect of changes in some LFS (1Hz, monophasic square wave) parameters (intensity, pulse duration and train duration) on piriform cortex kindled seizures was investigated both in fully kindled rats and during kindling acquisition. In fully kindled animals, application of different patterns of LFS immediately before kindling stimulation had no significant effect on seizure parameters. However, daily (15 min) application of LFS (0.1 ms pulse duration at intensity equal to after-discharge threshold (ADT) and 1 ms pulse duration at intensity equal to 1/4 ADT) during inter-seizure interval of 7 days significantly reduced the stage 5 duration of the next kindled seizure. Application of the same two LFS protocols for 3 days and 2 weeks had no effect on seizure parameters. The effect of LFS was also tested using different paradigms during kindling acquisition. When LFS (0.1 and 1 ms pulse duration, intensity equal to ADT and 1/4 ADT) was delivered daily after each kindling stimulation, it could significantly decrease after-discharge duration in various days during kindling development. In this experiment, only LFS with 0.1 ms pulse duration and intensity equal to ADT significantly delayed the appearance of seizure stages 1 and 2. According to obtained results, it may be concluded that in fully kindled rats application of different patterns of LFS before kindling stimulation has no anticonvulsant effect, but it can exert an inhibitory effect when applied during an inter-seizure interval of 7 days. In addition, LFS has antiepileptogenic effect during kindling acquisition. These effects depend on the applied LFS parameters (e.g. intensity, pulse duration and train duration).

Olfactory impairments in patients with unilateral cerebellar lesions are selective to inputs from the contralesional nostril.

Functional imaging studies of olfaction have consistently reported odorant-induced activation of the cerebellum. However, the cerebellar role in olfaction remains unknown. We examined the olfactory and olfactomotor abilities of patients with unilateral cerebellar lesions, comparing performance within subjects across nostrils, as well as between subjects with age-matched and young controls. Regarding olfactory performance, initial testing revealed that patients had a contralesional impairment in olfactory identification but not olfactory detection threshold. However, when tested under conditions that prevented compensatory sniffing strategies, the patients also exhibited a contralesional olfactory detection impairment. Regarding olfactomotor function, a healthy olfactomotor system generates sniffs that are (1) sufficiently vigorous and (2) inversely proportional to odorant concentration in sniff mean airflow velocity, maximum airflow velocity, volume, and duration. Patients' sniffs were lower in overall airflow velocity and volume in comparison with control participants. Furthermore, reduced sniff velocity predicted poorer detection thresholds in patients. Finally, whereas young controls used concentration-dependent sniffs, there was a trend in that direction only for age-matched controls. Patients used sniffs that were concentration invariant. In conclusion, cerebellar lesions impacted olfactory and olfactomotor performance. These findings strongly implicate an olfactocerebellar pathway prominent in odor identification and detection that functionally connects each nostril primarily to the contralateral cerebellum.

Magnetic resonance imaging predicts neuropathology from soman-mediated seizures in the rodent.

Intoxication by the organophosphate compound soman causes prolonged seizures that lead to neuropathology in the brain. This MRI-based study describes the temporal and spatial evolution of brain pathology that follows soman-induced convulsions. We observed significant decreases in apparent diffusion coefficients (ADC; 23% below control) of the hippocampus and thalamus by 12 h after soman treatment. The ADC then returned to near normal values in all regions at 24 h but declined again during the next 7 days. These data suggest that the initial cellular degradation may be resolved but is ultimately followed by regional cellular remodeling. T2 relaxation values declined significantly at 12 h (37% decrease) returning to near normal values by 24 h. These data lend detail to the model suggesting that injured tissues experience an edematous influx that is resolved by 24 h. The imaging data was fully supported by histopathological comparisons where moderate cell loss and swelling within the hippocampus and piriform cortex was observed. This is the first report providing excellenttemporal and spatial resolution of emerging soman-mediated, seizure-induced neuropathology using MRI with histological correlation.

Changes in Ca2+-dependent protein kinase C isoforms induced by chronic ethanol treatment in mice.

Protein kinase C (PKC) has been shown to regulate ethanol sensitivity. The goal of the present study was to ascertain whether chronic in vivo ethanol treatment could affect PKC isoforms in the mouse brain. We measured the protein level of membrane-bound PKC isoforms following chronic ethanol treatment using Western blotting. The protein level of membrane-bound PKCalpha and PKCgamma isoforms, which are defined as Ca2+-dependent PKC isoforms (cPKC), in the limbic forebrain during chronic ethanol treatment was significantly increased, whereas the levels of both were significantly decreased in the frontal cortex. By contrast, there was no change in PKCepsilon, a Ca2+-independent PKC isoform, in both areas. These findings suggest that the change in membrane-bound cPKC in the limbic forebrain and frontal cortex may play substantial roles for the development of ethanol dependence.

Retinoic acid enhances the rate of olfactory recovery after olfactory nerve transection.

In the olfactory system, retinoic acid (RA) plays an important role in development and may affect growth in the adult animal. To explore the potential effects of RA on recovery after injuries, adult mice were trained in a buried food paradigm and were given a single oral supplement of RA after olfactory nerve transection. Results demonstrate that RA accelerates the recovery of olfactory functions after injury.

Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain.

The excitatory amino acid glutamate has been implicated in the neurodegeneration associated with several different central nervous system diseases. Treatment with kainic acid (KA), a glutamate analog known to activate the AMPA/KA subtype of glutamate receptor, has been widely used as a model of epilepsy. Long term temporal studies of its neuropathological effects, however, are lacking. In this study, two techniques were used to directly visualize and characterize the neuropathology that occurred over a 2-month period following KA-induced status epilepticus in adult female Sprague-Dawley rats. Post-injection survival was 2, 4, 8 h, 2 days, 2 weeks, or 2 months. Labeling with Fluoro-Jade B (FJB), a fluorescent green dye that labels the cell body, dendrites, axons and axon terminals of degenerating neurons, was observed within the cortex, hippocampus, thalamus, basal ganglia, and amygdala by 4 h post-treatment. The highest level of labeling was seen in the piriform cortex, hippocampus, and thalamus. Myelin changes in the rat forebrain following KA treatment were also examined using the myelin-specific Black-Gold (BG) stain. Varicose myelinated fibers were observed in the same regions as FJB positive neurons, although these changes were evident by the 2-h survival time-point. Both stains showed a temporal progression of brain damage throughout the affected areas. By 2 months post-treatment, few degenerating neurons could be detected and abnormal myelin was absent in most regions. As myelin changes can be seen prior to neuronal degeneration, and oligodendrocytes express functional AMPA/kainate-type glutamate receptors, the neurodegeneration and myelin pathologies may occur as independent events. Thus, researchers should consider the temporal and multiple effects of kainic acid to optimize conditions for their endpoint of interest when designing experiments.

Alcohol exposure before pregnancy: effect on GABA levels and turnover in rat offspring.

The GABA levels and turnover rates in various brain areas from 2-month-old rats born to mothers who consumed 20% (v/v) alcohol during 1 month only before pregnancy, were investigated. A decreased level was found in the olfactory tubercules and an increase was observed in the hypothalamus. The turnover rates were reduced in both areas, whereas an increase was observed in the frontal cortex. These results indicate that biochemical alterations may occur in the offspring even if the fetus did not develop under alcoholization.