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The role of the cholinergic system with respect to cognitive deficits characteristic of Alzheimer's disease (AD) has led to a number of studies focusing on the development of acetylcholinesterase (AChE) inhibitors as a drug for treating this disease. The earliest known AChE inhibitors, namely, physostigmine and tacrine, performed poorly in clinical trials (e.g., poor oral activity, brain penetration, and hepatotoxic liability). Studies were then focused on finding a new type of acetylcholinesterase inhibitor that would overcome the disadvantages of these two compounds. Donepezil hydrochloride inaugurates a new class of AChE inhibitors with longer and more selective action and with manageable adverse effects.
Chem Rec 2001
PMID:Donepezil hydrochloride: a treatment drug for Alzheimer's disease. 1189 59

In humans, the pelvic floor skeletal muscles support the viscera. Damage to innervation of these muscles during parturition may contribute to pelvic organ prolapse and urinary incontinence. Unfortunately, animal models that are suitable for studying parturition-induced pelvic floor neuropathy and its treatment are rare. The present study describes the intrapelvic skeletal muscles (i.e., the iliocaudalis, pubocaudalis, and coccygeus) and their innervation in the rat to assess its usefulness as a model for studies of pelvic floor nerve damage and repair. Dissection of rat intrapelvic skeletal muscles demonstrated a general similarity with human pelvic floor muscles. Innervation of the iliocaudalis and pubocaudalis muscles (which together constitute the levator ani muscles) was provided by a nerve (the "levator ani nerve") that entered the pelvic cavity alongside the pelvic nerve, and then branched and penetrated the ventromedial (i.e., intrapelvic) surface of these muscles. Innervation of the rat coccygeus muscle (the "coccygeal nerve") was derived from two adjacent branches of the L6-S1 trunk that penetrated the muscle on its rostral edge. Acetylcholinesterase staining revealed a single motor endplate zone in each muscle, closely adjacent to the point of nerve penetration. Transection of the levator ani or coccygeal nerves (with a 2-week survival time) reduced muscle mass and myocyte diameter in the iliocaudalis and pubocaudalis or coccygeus muscles, respectively. The pudendal nerve did not innervate the intrapelvic skeletal muscles. We conclude that the intrapelvic skeletal muscles in the rat are similar to those described in our previous studies of humans and that they have a distinct innervation with no contribution from the pudendal nerve.
Anat Rec A Discov Mol Cell Evol Biol 2003 Nov
PMID:Innervation of the levator ani and coccygeus muscles of the female rat. 1453 77

Vertebrates are capable of producing a variable sound spectrum. In mammals, lissamphibia, and reptiles, the larynx is the vocal organ responsible for sound production, whereas in birds it is produced by the syrinx, an avian organ located at the base of trachea. The distribution of neuromuscular junctions responsible for the fine control of laryngeal muscle (LM) and syringeal muscle (SM), although studied with some detail in human LM, remains mostly unknown in other vertebrates. In the present study, we analyzed the distribution of motor end plates (MEPs) in LM/SM of different vertebrate classes using the histochemical detection of acetylcholinesterase: the thyroarytenoid and cricoarytenoid LM of mammal (human, rat, and rabbit) and cricoarytenoid LM of nonmammalian (frog and avian) species and the tracheobronchial SM of rooster and pigeon. In humans and frogs/avians, MEPs were distributed diffusely along, respectively, the thyroarytenoid-cricoarytenoid and the cricoarytenoid LM fibers, whereas in rats and rabbits, MEPs were concentrated in a transverse band located in the middle of thyroarytenoid and cricoarytenoid muscle fibers. In roosters and pigeons, MEPs were distributed diffusely along SM fibers. The highly diffuse MEP distribution along human thyroarytenoid and cricoarytenoid fibers indicates that these muscles can markedly change their degree of contraction, which may contribute for the large range of different sounds produced by human vocal folds. The same rationale was applied to discuss the possible functional significance of the morphological distribution of MEPs along the LM/SM of the other vertebrates analyzed.
Anat Rec A Discov Mol Cell Evol Biol 2006 May
PMID:Distribution of neuromuscular junctions in laryngeal and syringeal muscles in vertebrates. 1661 37

Anatomical and functional studies of the autonomic innervation in the lung of dipnoan fishes and the bichirs are lacking. The present immunohistochemical studies demonstrated the presence of nerve fibers in the muscle layers of the lung of the bichir, Polypterus bichir bichir, and identified the immunoreactive elements of this innervation. Tyrosine hydroxylase, acetylcholinesterase, and peptide immunoreactivity was detected in the intramural nerve fibers. Extensive innervation was present in the submucosa where adenylatecyclase/activating polypeptide 38, substance P, P(2)X(2), and 5-hydroxytryptamine (5-HT)-immunoreactive nerve fibers mainly supplied blood vessels. A collection of monopolar neurons located in the submucosal and the muscular layers of the glottis expressed a variety of various transmitters. These neurons may be homologous to ganglion cells in the branchial and pharyngeal rami of the vagus in fishes. Nerves containing 5-HT and P(2)X(2) receptor immunoreactivity projected to the lung epithelium. Associated with neuroepithelial cells in mucociliated epithelium, were neuronal nitric oxide synthase-immunopositive axons. The physiological function of this innervation is not known. The present study shows that the pattern of autonomic innervation of the bichir lung may by similar in its elements to that in tetrapods.
Anat Rec (Hoboken) 2007 Sep
PMID:Innervation and neurotransmitter localization in the lung of the Nile bichir Polypterus bichir bichir. 1772 50

Florida manatees have an extensive, well-developed system of vibrissae distributed over their entire bodies and especially concentrated on the face. Although behavioral and anatomical assessments support the manatee's reliance on somatosensation, a systematic analysis of the manatee thalamus and brainstem areas dedicated to tactile input has never been completed. Using histochemical and histological techniques (including stains for myelin, Nissl, cytochrome oxidase, and acetylcholinesterase), we characterized the relative size, extent, and specializations of somatosensory regions of the brainstem and thalamus. The principal somatosensory regions of the brainstem (trigeminal, cuneate, gracile, and Bischoff's nucleus) and the thalamus (ventroposterior nucleus) were disproportionately large relative to nuclei dedicated to other sensory modalities, providing neuroanatomical evidence that supports the manatee's reliance on somatosensation. In fact, areas of the thalamus related to somatosensation (the ventroposterior and posterior nuclei) and audition (the medial geniculate nucleus) appeared to displace the lateral geniculate nucleus dedicated to the subordinate visual modality. Furthermore, it is noteworthy that, although the manatee cortex contains Rindenkerne (barrel-like cortical nuclei located in layer VI), no corresponding cell clusters were located in the brainstem ("barrelettes") or thalamus ("barreloids").
Anat Rec (Hoboken) 2007 Sep
PMID:Somatosensory nuclei of the manatee brainstem and thalamus. 1772 80

The neuroanatomy of the ileocecal valve (ICV) is poorly understood. A better understanding of this important functional component of the gastrointestinal tract would enable surgeons to reconstruct an effective valve following surgical resection of the ICV. ICVs were examined in young pigs (N = 5) using frontal and transverse paraffin embedded and frozen sections. Hematoxylin+Eosin (H+E) staining, acetylcholinesterase (AchE), and NADPH-diaphorase (NADPH-d) histochemistry and protein gene product 9.5 (PGP 9.5) and C-kit immunohistochemistry were performed. The H+E staining revealed that the ICV consists of three muscle layers: an external circular muscle layer continuous with that of the ileal circular muscle layer, an inner circular muscle layer continuous with that of the cecal circular muscle layer, and a single longitudinal muscle layer, which appears to be secondary to a fusion of the ileal and cecal longitudinal muscle layers. The AchE, NADPH-d, and PGP 9.5 staining revealed two distinct coaxial myenteric plexuses, together with superficial and deep submucosal plexuses. The C-kit immunostaining showed a continuous myenteric ICC network within the ICV. The structure of the neuromuscular components within the ICV suggests that the valve is a result of a simple intussusception of the terminal ileum into the cecum. This knowledge may help surgeons in their future attempts at reconstructing more anatomically and functionally suitable ICVs following surgical resection of native ICVs.
Anat Rec (Hoboken) 2009 Feb
PMID:New insights into the neuromuscular anatomy of the ileocecal valve. 1908 3

From postnatal-day-0 to postnatal-day-2, a few acetylcholinesterase (AChE)-active and choline acetytransferase (ChAT)-immunoreactive nerve fibers and relatively numerous vesicular acetylcholine transporter (VAChT)-immunoreactive puncta were observed in the rat adrenal medulla. Despite relatively numerous clear vesicles in the nerve fibers, the synthesis and hydrolysis of acetylcholine may not be fully activated until postnatal-day-2. The number of AChE-active and ChAT-immunoreactive nerve fibers dramatically increased and that of VAChT-immunoreactive puncta gradually increased from postnatal-day-3 to postnatal-week-1. The synthesis and hydrolysis of acetylcholine may be dramatically activated in the nerve fibers of the medulla until postnatal-week-1. From postnatal-week-2 to postnatal-week-3, the number of AChE-active and the ChAT-immunoreactive nerve fibers gradually increased and reached the adult levels. The VAChT-immunoreactive puncta per unit area was maximum number at postnatal-week-2. The synthesis and hydrolysis of acetylcholine in the nerve fibers of the medulla may be completed between postnatal-week-2 to postnatal-week-3. The diameter of the VAChT-immunoreactive puncta gradually increased from postnatal-day-0 with aging. However, the number of the VAChT-immunoreactive puncta gradually decreased from postnatal-week-2 onwards. In electron-microscopy, the VAChT-immunoreactive deposits were seen in clusters of clear vesicles, and the diameter of the nerve fibers and the number of clear vesicles at postnatal-week-8 increased compared with those at postnatal-week-2. The AChE-active, ChAT-immunoreactive, and VAChT-immunoreactive nerve fibers observed around noradrenaline (NA) cells were denser than those around adrenaline (A) cells in the medulla at postnatal-week-8. These suggest that the preferential innervation of NA and A cells may cause the differential secretion NA and A.
Anat Rec (Hoboken) 2009 Mar
PMID:Acetylcholinesterase activity, choline acetyltransferase and vesicular acetylcholine transporter immunoreactivities in the rat adrenal gland during postnatal development. 1924 56

Although the morphology of human lumbar transversospinal (TSP) muscles has been studied, little is known about the structure of these muscles in the mouse (Mus musculus). Such information is relevant given mice are often used as a "normal" phenotype for studies modeling human development. This study describes the gross morphology, muscle fiber arrangement, and innervation pattern of the mouse lumbar TSP muscles. A unique feature of the study is the use of a transgenic mouse line bearing a muscle-specific nuclear marker that allows clear delineation of muscle fiber and connective tissue boundaries. The lumbar TSP muscles of five mice were examined bilaterally; at each spinal level muscles attached to the caudal edge of the spinous process and passed caudally as a single complex unit. Fibers progressively terminated over the four vertebral segments caudad, with multiple points of muscle fiber attachment on each vertebra. Motor endplates, defined with acetylcholinesterase histochemistry, were consistently located half way along each muscle fiber, regardless of length, with all muscle fibers arranged in-parallel rather than in-series. These results provide information relevant to interpretation of developmental and functional studies involving this muscle group in the mouse and show mouse lumbar TSP muscles are different in form to descriptions of equivalent muscles in humans and horses.
Anat Rec (Hoboken) 2010 Dec
PMID:Morphology of the lumbar transversospinal muscles examined in a mouse bearing a muscle fiber-specific nuclear marker. 2108 41

Sternocleidomastoid (SCM) is a long muscle with two bellies, sternomastoid (SM) and cleidomastoid (CM) in the lateral side of the neck. It has been widely used as muscle and myocutaneous flap for reconstruction of oral cavity and facial defects and as a candidate for reinnervation studies. Therefore, exact neuroanatomy of the SCM is critical for guiding reinnervation procedures. In this study, SM in rats were investigated to document banding pattern of motor endplates (MEPs) using whole-mount acetylcholinesterase (AChE) staining and to determine locations of the motoneurons innervating the muscle using retrograde horseradish peroxidase (HRP) tracing technique. The results showed that the MEPs in the SM and CM were organized into a single band which was located in the middle portion of the muscle. After HRP injections into the MEP band of the SM, ipsilaterally labeled motoneurons were identified in the caudal medulla oblongata (MO), C1, and C2. The SM motoneurons were found to form a single column in lower MO and dorsomedial (DM) nucleus in C1. In contrast, the labeled SM motoneurons in C2 formed either one (DM nucleus), two [DM and ventrolateral (VL) nuclei], or three [DM, VL, and ventromedial (VM)] columns. These findings are important not only for understanding the neural control of the muscle but also for evaluating the success rate of a given reinnervation procedure when the SM is chosen as a target muscle.
Anat Rec (Hoboken) 2011 Feb
PMID:Locations of the motor endplate band and motoneurons innervating the sternomastoid muscle in the rat. 2123 5

We have used the histochemical and immunohistochemical staining methods and maps of gene expression to analyze the structure of the inferior olive of the C57BL mouse. As in other mammals, the inferior olive of the C57BL mouse contains three major nuclei, the medial nucleus, the principal nucleus, and the dorsal nucleus. The medial nucleus can be divided into a rostral medial nucleus and a more complex caudal part, which is formed by subnuclei C, B, A, the cap of Kooy, and the beta subnucleus. The principal nucleus includes the major principal nucleus and the arcuate subnucleus. Most of the inferior olive neurons are small to medium size, the smallest of which are found in the arcuate subnucleus. Calbindin and the vesicular glutamate transporter 2 gene are expressed in nearly all inferior olive neurons, but acetylcholinesterase, glutamate decarboxylase 1 gene, cocaine- and amphetamine-regulated transcript protein prepropeptide gene, galanin gene, and calretinin are selectively expressed within different subnuclei. These findings are consistent with a pattern of extensive functional differentiation among the neuron groups of the inferior olive.
Anat Rec (Hoboken) 2014 Feb
PMID:The inferior olive of the C57BL/6J mouse: a chemoarchitectonic study. 2444 86


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