ADHD pathogenesis in the immune, endocrine and nervous systems of juvenile and maturating SHR and WKY rats.

RATIONALE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioural disorders with morphological and functional brain abnormalities. However, there is a growing body of evidence that abnormalities in the immune and endocrine systems may also account for the ADHD pathogenesis. OBJECTIVES: To test ADHD pathogenesis in neurological, immune and endocrine systems, this study examined the concentrations of cytokines, chemokines, oxidative stress markers, metabolic parameters, steroid hormones and steroidogenic enzymes in the serum and/or tissues of spontaneously hypertensive rats (SHRs, animal model of ADHD) and Wistar Kyoto rats (WKYs, control animals). Moreover, the volume of the medial prefrontal cortex (mPFC) as well as the density of dopamine 2 (D2) receptor-expressing cells and tyrosine hydroxylase (TH)-positive nerve fibres in it was also elucidated. METHODS: Peripheral blood, spleen and adrenal gland samples, as well as brain sections collected on day 35 (juvenile) and day 70 (maturating) from SHRs and WKYs, were processed by ELISA and immunohistochemistry, respectively. RESULTS: The results show significant increases of serum and/or tissue concentrations of cytokines, chemokines and oxidative stress markers in juvenile SHRs when compared to the age-matched WKYs. These increases were accompanied by a lowered volume of the mPFC and up-regulation of D2 in this brain region. In maturating SHRs, the levels of inflammatory and oxidative stress markers were normalised and accompanied by elevated contents of steroid hormones. CONCLUSIONS: Significant elevations of serum and/or tissue contents of cytokines, chemokines and oxidative stress markers as well as volumetric and neurochemical alterations in the mPFC of juvenile SHRs may suggest the cooperation of neurological and immune systems in the ADHD pathogenesis. Elevated levels of steroid hormones in maturating SHRs may be a compensatory effect involved in reducing inflammation and ADHD symptoms.

Diagnosis and Incidence of Spondylosis and Cervical Disc Disorders in the University Clinical Hospital in Olsztyn, in Years 2011-2015.

BACKGROUND: Disorders connected with the musculoskeletal and central nervous system dysfunction are the most significant clinical problem worldwide. Our earlier research has shown that back and spinal disorders and lumbar disc disorders were most frequently diagnosed using MRI scanner at the University Clinical Hospital (UCH) in Olsztyn in years 2011-2015. We have also observed that another two diseases of spinal column, spondylosis and cervical disc disorders, were also very prevalent. The main objective of this work was to analyze the prevalence of spondylosis and cervical disc disorders in the study population diagnosed at UCH in years 2011-2015. METHODS: The digital database including patients' diagnostic and demographic information was generated based on MRI reports from years 2011-2015 and analyzed using SPSS software. RESULTS: Within the study group (n = 13298) the most frequently MRI-diagnosed diseases were musculoskeletal group (M00-M99; n = 7711; 57,98%) and cervical disc disorders (M50; n = 1659; 12,47%) and spondylosis (M47, n = 611; 4,59%). More women (67%) than men (33%) were enrolled in the study, and the largest fraction of the study population was in the range of 51-60 years, with about 1/3 of cases of both diseases diagnosed in early age range of 31-40 years. CONCLUSION: Significant number of patients presenting with either of the spine disorders at the young age of 31-40 years points to the necessity of introducing methods preventing disorders of the vertebral column at younger age, preferably at school age.

Parvalbumin, but not calretinin, neurons express high levels of α1-containing GABAA receptors, α7-containing nicotinic acetylcholine receptors and D2-dopamine receptors in the basolateral amygdala of the rat.

The generation of emotional responses by the basolateral amygdala is largely determined by the balance of excitatory and inhibitory inputs to its principal neurons - the pyramidal cells. The activity of these neurons is tightly controlled by g-aminobutyric acid (GABA)ergic interneurons, especially by those expressing parvalbumin (PV) and calretinin (CR). Although it is known that GABAergic, cholinergic and dopaminergic fibres make synapses on PV and CR cells, knowledge of the various receptors which are used by these cells is still incomplete. Thus, the present study investigates whether neurons expressing PV or CR co-express specific GABA, acetylcholine and/or dopamine receptors in the basolateral amygdala of the rat. The results show that almost two-thirds of PV neurons co-express high concentrations of α1 subunit of GABAA receptor, and more than half of them co-express high levels of α7 subunit of nicotinic acetylcholine receptor and/or D2-subtype of dopamine receptor. In contrast, a smaller percentage of CR neurons had detectable amounts of these receptors and at lower levels of abundance in most cases. In conclusion, the present results indicate that not only principal neurons but also GABAergic interneurons have specific receptors, which allow these cells to respond to the GABAergic, cholinergic and dopaminergic inputs coming to the basolateral amygdala of the rat. Since these cells receive intrinsic GABAergic inputs, they are strongly interconnected. Since they also receive extrinsic cholinergic and dopaminergic inputs, such stimulation may result in stimulus-driven feed-forward control of the principal neurons. The effects of such control may be either feed-forward inhibition of the principal neurons via α7 nicotinic acetylcholine receptors or disinhibition of these cells via D2-dopamine receptors.

Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.

In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed.

Distribution and chemical coding pattern of the cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in the preoptic area of the pig.

This study provides a detailed description of cocaine-and amphetamine-regulated transcript (CART) distribution and the co-localization pattern of CART and gonadotropin releasing hormone (GnRH), somatostatin (SOM), neuropeptide Y (NPY), cholecystokinin (CCK), and substance P (SP) in the preoptic area (POA) of the domestic pig. The POA displays a low density of immunoreactive cells and rich immunoreactivity for CART in fibers. CART-immunoreactive (CART-IR) cell bodies were single and faintly stained, and located in the medial preoptic area (MPA) and the periventricular region of the POA. A high density of immunoreactive fibers was observed in the periventricular preoptic nucleus (PPN); a high to moderate density of fibers was observed in the MPA; but in the dorso-medial region of the MPA the highest density of fibers in the whole POA was observed. The lateral preoptic area (LPA) exhibited a less dense concentration of CART-immunoreactive fibers than the MPA. The median preoptic nucleus (MPN) showed moderate to low expression of staining fibers. In the present study, dual-labeling immunohistochemistry was used to show that CART-IR cell bodies do not contain any GnRH and SP. CART-positive fibers were identified in close apposition with GnRH neurons. This suggests that CART may influence GnRH secretion. Double staining revealed that CART-IR structures do not co-express any of the substances we studied, but a very small population of CART-IR fibers also contain SOM, CCK or SP.

Somatostatin-like immunoreactivity in the amygdala of the pig.

The distribution and morphology of neurons containing somatostatin (SOM) was investigated in the amygdala (CA) of the pig. The SOM-immunoreactive (SOM-IR) cell bodies and fibres were present in all subdivisions of the porcine CA, however, their number and density varied depending on the nucleus studied. The highest density of SOM-positive somata was observed in the layer III of the cortical nuclei, in the anterior (magnocellular) part of the basomedial nucleus and in the caudal (large-celled) part of the lateral nucleus. Moderate to high numbers of SOM-IR cells were also observed in the medial and basolateral nuclei. Many labeled neurons were also consistently observed in the lateral part of the central nucleus. In the remaining CA regions, the density of SOM-positive cell bodies varied from moderate to low. In any CA region studied SOM-IR neurons formed heterogeneous population consisting of small, rounded or slightly elongated cell bodies, with a few poorly branched smooth dendrites. In general, morphological features of these cells clearly resembled the non-pyramidal Golgi type II interneurons. The routine double-labeling studies with antisera directed against SOM and neuropeptide Y (NPY) demonstrated that a large number of SOM-IR cell bodies and fibers in all studied CA areas contained simultaneously NPY. In contrast, co-localization of SOM and cholecystokinin (CCK) or SOM and vasoactive intestinal polypeptide (VIP) was never seen in cell bodies and fibres in any of nuclei studied. In conclusion, SOM-IR neurons of the porcine amygdala form large and heterogeneous subpopulation of, most probably, interneurons that often contain additionally NPY. On the other hand, CCK- and/or VIP-IR neurons belonged to another, discrete subpopulations of porcine CA neurons.