Genetic Targeting in Cerebellar Purkinje Cells: an Update

Since the last review paper published in Cerebellum in 2002 [1], there has been a substantial increase in the number of experiments utilizing transgenic manipulations in murine cerebellar Purkinje cells. Most of these approaches were made possible with the use of the Cre/loxP methodology and pcp2/L7 based Cre recombinase expressing transgenic mouse strains. This review aims to summarize all studies which used Purkinje cell specific transgenesis since the first use of mouse strain with Purkinje cell specific Cre expression in 2002

The quality of life at patients with the extrapyramidal system diseases after stereotactic surgery and rehabilitation

INTRODUCTION Nowadays the functional neurosurgery makes up the recognized strategy of proceeding in the treatment: Parkinson diseases (PD), tremor, and generalized dystonia. According to directive line of American Physical Therapy Association´s the main role of physiotherapist is creating individual rehabilitation programs and their incessant modification in relation to changing condition of patient. MATERIAL AND METHODS Patients were hospitalized in Department of Neurosurgery Medical University of Silesia in Katowice. The surgical treatment of extrapyramidal system diseases and rehabilitation after surgery were applied to 36 persons. The average age was 58,8 years. The proportional part of diagnosis in the analyzed material: (PD)-58%, tremor-28%, dystonia-14%. The average period of the observation and length of disease were: 44,6 and 142,3 month. For evaluation of quality of life PDQ-39 questionnaire and EQ-5D (EuroQol) questionnaire were used. RESULTS The results of investigations were elaborated in the aim of comparison of the quality of life in relation to applied surgical treatment and after surgery rehabilitation. The results proved the statistically essential influence of rehabilitation on: mobility, pain and usual activities (EQ-5D) questionnaire. The regress analyses showed the essential, negative influence of length disease on EQ-5D assessment. CONCLUSIONS Rehabilitation and the type of diagnosis influence essentially on the quality of life at persons after stereotactic surgery performed because of extrapyramidal system diseases.WSTĘP Neurochirurgia czynnościowa oraz następujący bezpośrednio po niej proces rehabilitacji, zgodny wytycznymi American Physical Therapy Association’s stanowią obecnie uznaną strategię postępowania w leczeniu choroby Parkinsona, drżenia i uogólnionych dystonii. MATERIAŁ I METODY Badaniem objęto 36 osób hospitalizowanych w Klinice Neurochirurgii SUM w Katowicach. Materiał badawczy stanowiło 21 chorych z chorobą Parkinsona w wieku średnio 60,3 lat, 10 osób z drżeniem samoistnym w wieku średnio 61,1 lat oraz 5 osób z dystonią, w wieku średnio 47,6. Okres obserwacji i czas trwania choroby wyniosły średnio: 44,6 i 142,3 miesiąca, odpowiednio: 27,7 i 144,5 - choroba Parkinsona, 41 i 130,2 - drżenie, 123,4 i 157,2 – dystonia. W pracy posłużono się subiektywnymi skalami oceny jakości życia: skalą EQ-5D (EuroQol ), oraz PDQ-39. WYNIKI Z przeprowadzonych badań wynika, że rodzaj rozpoznania (w szczególności choroba Parkinsona) wpływa istotnie na uzyskiwane przez pacjentów oceny jakości życia (PDQ-39, EQ-5D). Zauważono również znaczący wpływ rodzaju pooperacyjnej rehabilitacji na uzyskiwane wyniki. Nie stwierdzono bezpośredniego wpływu rodzaju zabiegu chirurgicznego na ostateczną ocenę jakości życia chorych. Uzyskane wyniki potwierdzają badania innych autorów dotyczące wpływu konkretnych metod oraz programów rehabilitacyjnych na odległe wyniki postępowania leczniczego u pacjentów z wyżej wymienionymi jednostkami chorobowymi. WNIOSKI Rehabilitacja oraz rodzaj postawionego rozpoznania warunkują jakość życia pacjentów ze schorzeniami układu pozapiramidowego po zastosowaniu nowoczesnych metod leczenia chirurgicznego

Central Angiotensin Type 2 Receptor (AT2R) Stimulation Promotes Enhanced Extinction of Fear Learning Independent of Cardiovascular Measures

Angiotensin II receptor subtypes (AT1R and AT2R) are found in regions of the brain critical to the expression and extinction of conditioned fear, however the neurobiological role(s) remain unknown. We propose that brain angiotensin receptors contribute to modulating inhibitory and excitatory conditioned fear circuits, that maybe important in the pathology of posttraumatic stress disorder (PTSD). The objective of this study was to investigate the role of brain AT2R activation in fear memory. To study learned fear, C57BL/6 J mice (n= 6-10 / group) underwent classical Pavlovian fear conditioning, pairing auditory cues with foot shocks. The neural circuitry underlying the fear response is highly conserved across mammalian species, making rodent models a valuable tool in the study of fear learning disorders, such as PTSD. The percentage of time spent freezing in response to a conditioned stimulus is used to quantify the ability to learn and remember fearful associations. Using this model, the expression of learned fear is tested 24 hours after conditioning, and memory retention one day later. Following the acquisition of fear, AT2R mRNA expression was elevated in the central amygdala (CeA) (t(22) = 2.5; p\u3c0.05), a critical region involved in the consolidation of fear memory. To further evaluate the functional role of brain AT2R, we administered (intra-cerebral ventricle - ICV) the highly selective AT2R agonist Compound 21 (C21-Vicore Pharma). A single ICV injection of C21 at either 0.06ug/ul or 0.1ug/ul was administered prior to fear expression testing. Acute C21 (0.1ug/ul) treated mice showed a significant reduction in both fear expression (% freezing) (saline – 62.5% vs C21 - 41.2%) (t(27) = 2.8; p\u3c0.05) and fear memory retention (saline – 52.9% vs C21 – 22.6%) (t(28) = 3.8; p\u3c0.05) following the acquisition of fear. Similarly, mice receiving C21 ICV for 2 weeks showed a trend for a reduction in fear memory retention (saline – 57.2% vs C21 – 39.6%) (t(14) = 1.0; p=0.06 and this was independent of behavioral measures of anxiety as determined by open field testing. Moreover, C21 did not affect blood pressure or heart rate in telemetry-implanted mice (Saline-144 ± 3 SBP mmHg, HR 507 ± 13 bpm, n=5; C21 - 136 ± 3 SBP mmHg; HR 518 bpm ± 26, n=4). These data suggest that activation of central AT2 receptors promote the extinction of learned fear. Further studies are required to determine the neurobiological mechanism(s), which may involve changes in cerebral vascular blood flow and/or modulation of neuronal excitability and plasticity

Impaired Autonomic Regulation in Posttraumatic Stress Disorder

Post-­traumatic stress disorder (PTSD) is associated with a significantly increased risk of cardiovascular disease (CVD) and accumulating clinical evidence suggests that autonomic dysregulation due to sympathetic overactivity and/or parasympathetic insufficiency may contribute to progression of CVD in PTSD. Therefore, utilizing a translational approach, we sought to examine autonomic function in both a clinical PTSD population as well as in an animal model of PTSD. In experimental studies, mice were instrumented with radiotelemetry probes to evaluate autonomic indices following Pavlovian fear conditioning. Fear conditioning involves the pairing of a conditioned stimulus (e.g. tone) paired with an aversive uconditioned stimulus (e.g. foot shock) that evokes a conditioned response (e.g. freezing). Twenty-­four hours following fear conditioning, spectral analysis of heart rate was performed and the low-­to high-­frequency ratio (LF:HF) was used as an index of sympathovagal balance. Fear conditioned animals displayed a significant increase in the LF:HF ratio relative to baseline (1.21 ± 0.46;; pfall in blood pressure compared to control (Δ Systolic -­71.7± 1.9 vs -­39.8 ± 5.8 mmHg;; p24-­hour ambulatory BP measurements have been collected at rest, during, and following mental stress. In an effort to translate our pre-­clinical results, these data will be analyzed for spectral analysis of heart rate variability, BP variability, and 24-­hour ambulatory BP patterns. Support or Funding Information NIH R00 HL107675-­03 American Heart Association -­ 15CSA2434000

Autonomic and Inflammatory Consequences of Posttraumatic stress disorder (PTSD) and the Link to Cardiovascular Disease.

Stress- and anxiety-related disorders are on the rise in both military and general populations. Over the next decade, it is predicted that treatment of these conditions, in particular, posttraumatic stress disorder (PTSD), along with its associated long-term comorbidities, will challenge the health care system. Multiple organ systems are adversely affected by PTSD, and PTSD is linked to cancer, arthritis, digestive disease, and cardiovascular disease. Evidence for a strong link between PTSD and cardiovascular disease is compelling, and this review describes current clinical data linking PTSD to cardiovascular disease, via inflammation, autonomic dysfunction, and the renin-angiotensin system. Recent clinical and preclinical evidence regarding the role of the renin-angiotensin system in the extinction of fear memory and relevance in PTSD-related immune and autonomic dysfunction is also addressed

Angiotensin II Type 2 Receptor-Expressing Neurons in the Central Amygdala Influence Fear-Related Behavior

BACKGROUND: The renin-angiotensin system has been implicated in posttraumatic stress disorder; however, the mechanisms responsible for this connection and the therapeutic potential of targeting the renin-angiotensin system in posttraumatic stress disorder remain unknown. Using an angiotensin receptor bacterial artificial chromosome (BAC) and enhanced green fluorescent protein (eGFP) reporter mouse, combined with neuroanatomical, pharmacological, and behavioral approaches, we examined the role of angiotensin II type 2 receptor (AT METHODS: Dual immunohistochemistry with retrograde labeling was used to characterize AT RESULTS: AT CONCLUSIONS: These findings suggest that CeM A

The Modification of the Ketogenic Diet Mitigates Its Stunting Effects in Rodents

The high fat and low carbohydrate ketogenic diet (HFKD) is extensively studied within the fields of numerous diseases, including cancer and neurological disorders. Since most studies incorporate animal models, ensuring the quality of ketogenic rodent diets is important, both in the context of laboratory animal welfare as well as for the accuracy of the obtained results. In this study we implemented a modification to a commonly-used ketogenic rodent chow by replacing non-resorbable cellulose with wheat bran. We assessed the effects of month-long treatment with either the unmodified or the modified HFKD on the growth and development of young male rats. Daily body weight, functional performance, and brain morphometric parameters were assessed to evaluate the influence of both applied diets on rodent development. Our results revealed that the unmodified ketogenic chow induced strong side effects that included weakness, emaciation, and brain undergrowth concomitant to growth inhibition. However, application of the ketogenic chow supplemented with wheat bran suppressed these adverse side effects, which was associated with the restoration of insulin-like growth factor 1 and a decrease in corticosterone levels. We have also shown that the advantageous results of the modified HFKD are not species- or sex-specific. Our data indicate that the proposed HFKD modification even allows for its application in young animals, without causing detrimental side effects.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author