Astaxanthin and DHA Supplementation Modulates the Maternal Undernutrition-induced Impairment of Cognitive Behavior and Synaptic Plasticity in Adult Life of Offspring's -Exploring the Molecular Mechanism.

Maternal nutrition was recognized as a significant part of brain growth and maturation in most mammalian species. Timely intervention with suitable nutraceuticals would provide long-term health benefits. We aim to unravel the molecular mechanisms of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated undernourished dams at their gestational, lactational, and at both the time point with Astaxanthin (AsX) and Docosahexaenoic acid (DHA), and their pups were used as experimental animals. We evaluated the cognitive function by subjecting the pups to behavioral tests in their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and uncoupling protein-2 (UCP2) gene expression in pups born to undernourished dams in their adult life, which AsX and DHA modulated. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) tasks in offspring's. The expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control and AsX-DHA treated groups at CA1, CA2, CA3, and DG. AsX and DHA supplementation upregulated BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished rats, which are involved in intracellular signaling cascades like Ras, PI3K, and PLC. The results of our study give new insights into neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing maternal undernutrition-induced cognitive impairment in offspring's.

Playback of 22-kHz and 50-kHz ultrasonic vocalizations induces differential c-fos expression in rat brain.

Rodent ultrasonic vocalizations, which serve as sensitive measures in a number of relevant individual and social behaviours, have become increasingly interesting for biopsychological studies on emotion and motivation. Of these, high frequency (50-kHz) ultrasonic vocalizations can index a positive emotional state, and induce approach, whereas low frequency (22-kHz) ultrasonic vocalizations can induce avoidance and may index anxiety, since they are emitted during various unconditioned and conditioned aversive situations. While cholinergic and dopaminergic systems have been implicated, specific neural substrates that sub-serve these vocalization-dependent states remain to be elucidated. Using c-fos immunocytochemistry, we revealed neural activity in brain areas of naïve male Wistar rats in response to playback of 22-kHz and flat and frequency-modulated 50-kHz ultrasonic vocalizations. Presentation of background noise or no acoustic stimulus at all constituted the controls. Playback of 50-kHz ultrasonic vocalizations led to approach behaviour. Acoustically stimulated animals demonstrated differential activation in auditory areas, with a frequency-dependent activation in the auditory cortex. Specific forebrain, thalamic, hypothalamic and brainstem areas were also activated differentially. While 50-kHz playback induced sparse fos-like immunoreactivity in frontal association cortex, nucleus accumbens, thalamic parafascicular and paraventricular nuclei, 22-kHz playback elicited c-fos expression in the perirhinal cortex, amygdalar nuclei and the periaqueductal gray. This study unveils neural substrates that are activated during ultrasonic playback perception, which could sub-serve the affective states elicited by these vocalizations.

Afferentation of the lateral nidopallium: A tracing study of a brain area involved in sexual imprinting in the zebra finch (Taeniopygia guttata).

The lateral forebrain of zebra finches that comprises parts of the lateral nidopallium and parts of the lateral mesopallium is supposed to be involved in the storage and processing of visual information acquired by an early learning process called sexual imprinting. This information is later used to select an appropriate sexual partner for courtship behavior. Being involved in such a complicated behavioral task, the lateral nidopallium should be an integrative area receiving input from many other regions of the brain. Our experiments indeed show that the lateral nidopallium receives input from a variety of telencephalic regions including the primary and secondary areas of both visual pathways, the globus pallidus, the caudolateral nidopallium functionally comparable to the prefrontal cortex, the caudomedial nidopallium involved in song perception and storage of song-related memories, and some parts of the arcopallium. There are also a number of thalamic, mesencephalic, and brainstem efferents including the catecholaminergic locus coeruleus and the unspecific activating reticular formation. The spatial distribution of afferents suggests a compartmentalization of the lateral nidopallium into several subdivisions. Based on its connections, the lateral nidopallium should be considered as an area of higher order processing of visual information coming from the tectofugal and the thalamofugal visual pathways. Other sensory modalities and also motivational factors from a variety of brain areas are also integrated here. These findings support the idea of an involvement of the lateral nidopallium in imprinting and the control of courtship behavior.

Enhanced fos expression in the zebra finch (Taeniopygia guttata) brain following first courtship.

Young zebra finch males that court a female for the first time develop a stable preference for the females of that species. On the neuronal level, consolidation of the imprinted information takes place. Here we demonstrate that first courtship or being chased around in the cage leads to enhanced fos expression in forebrain areas implicated in learning and imprinting in zebra finch males compared with birds reared in isolation or in the aviary. Two of the forebrain areas highly active during first courtship (as demonstrated by the 14C-2-deoxyglucose technique), the imprinting locus latral neo/hyperstriatum ventrale (LNH) and the secondary visual area hyperstriatum accessorium/dorsale (HAD), demonstrate enhanced fos expression. Two other imprinting-related areas, the medial neo/hyperstriatum ventrale (MNH) and archistriatum/neostriatum caudale (ANC), do show c-fos induction; however, the areas are not congruous with those demarcated by the 2-DG autoradiographic studies. Additional telencephalic areas include the olfactory lobe, the information storage site lobus parolfactorius (LPO), the memory site hippocampus, the auditory caudomedial neostriatum implicated in the strength of song learning, and the caudolateral neostriatum, which is comparable to the mammalian prefrontal cortex. In addition, c-fos is induced by first courtship and chasing in neurosecretory cell groups of the preoptic area and hypothalamus associated with the repertoire of sexual behavior and stress or enhanced arousal. Enhanced fos expression is also observed in brainstem sources of specific (noradrenergic, catecholaminergic) and nonspecific (reticular formation) activating pathways with inputs to higher brain areas implicated in the imprinting process. Birds reared in isolation or alternatively in the aviary with social and sexual contact to conspecifics showed attenuated or no fos expression in most of the above-mentioned areas. First courtship and chasing both lead to enhanced uptake of 2-DG in the four imprinting areas, as well as subsequent changes in spine density-an anatomical manifestation of the imprinting process. fos expression in the imprinting and other telencephalic, preoptic, hypothalamic, and mesencephalic brain regions indicates processing of stimuli originating from exposure (like chasing) and the analysis of stimuli in a behaviorally relevant, sexually explicit context (like first courtship). c-fos induction in these brain areas indicates its involvement in the triggering of neural changes that accompany the learning process of imprinting, leading eventually to alterations in dendritic spine density in the zebra finch.